DISCLAIMER--PLEASE READ

While every attempt has been made to have dosages, medications, and treatment recommendations as accurate and up to date as possible, this manual is no substitute for clinical judgement and knowledge. The authors are not liable for any action taken on the basis of this manual.

RETINA


Revised by Jonathan Gerald Williams, M.D.
Editor Balaji Gupta M.D.
Edited by Meagan Celmer M.D.



  • Basics

    • Layers (inner to outer):
      • Inner limiting membrane
      • Nerve fiber layer
      • Ganglion cell layer
      • Inner plexiform layer (bipolar/amacrine w/ ganglion cells)
      • Inner nuclear layer (bipolar, Muller, horizontal, amacrine)
      • Outer plexiform layer (photoreceptors w/ horizontal/bipolar)
      • Outer nuclear layer (photoreceptor nuclei)
      • External limiting membrane
      • Photoreceptors – inner & outer segments
      • RPE
    • Macula
      • 5.5 mm in diam. (3.5 mm or 18o of visual angle) centered 4 mm temp and 0.8 mm inf. to center of optic disc
    • Fovea:
      • Concave central retinal depression 1.5 mm in diam. (1 DD or 5o)
    • Foveola:
      • 0.35 mm in diam. - FAZ
    • Umbo (clivus): central concavity of foveola floor / light reflex


    • Neurosensory retinal thickness
      • 0.23 mm - papillomacular bundle near optic nerve
      • 0.11 mm - ora serrata
      • 0.10 mm - foveola
    • Retinal circulation
      • CRA supplies inner retina incl. inner 1/3 of INL
      • Choriocapillaris (CC) supplies outer 2/3 of INL to RPE
    • Bruch’s Membrane
      • Layers (inner to outer)
        • BM of RPE
        • Inner collagenous zone
        • Elastin layer
        • Outer collagenous zone
        • BM of CC endothelium



    • RPE
      • Functions
        • Physical
          • Forms outer blood-ocular barrier
          • Adhesion of neurosensory retina via pump
          • Vit A metabolism
        • Optical
          • Melanin granules absorb light energy to reduce scatter and enhance image resolution
        • Metabolic
          • Phagocytosis of photoreceptor outer segments
          • Metabolite transport
          • Atrophic, hypertrophic and hyperplastic responses to dz


  • II. Diagnostic Approach to Retinal Disease


    • Fluorescein angiography
      • White light>blue filter>blue light (490nm) enters eye and stimulates fluorescein molecules to emit yellow-green light (530nm) with reflected blue light>yellow-green filter on camera blocks reflected blue light and transmits yellow-green light>image recorded on B&W high contrast film
      • Hypofluorescence:
        • blockage, filling defect/inadequate perfusion
      • Hyperfluorescence:
        • leakage, staining, pooling, transmission of fluorescence, autofluorescence
    • ICG
      • Fluoresces at 835 nm, detectable by video angiography
      • Fluoresces through pigment and hemorrhage
      • Useful to detect CNV
      • Do not use in pts. allergic to iodine, shellfish

    • Retinal neovascularization
      • Vessels grow inward through ILM, along posterior surface of vitreous or into cortical vitreous
      • Requires:
        • angiogenic stimulus (presumably from ischemia/inflammation)
        • source of viable endothelial cells from existing retinal or optic nerve blood vessels,
        • +/- intact posterior cortical vitreous

    • Choroidal Neovascularization (CNV)
      • May occur in any ocular condition affecting integrity of CC/Bruch’s MB/RPE/outer retina complex:


Causes of CNV
Examples
Degenerative
AMD
Myopic degneration
Angioid Streaks
Heredodegenerative
Best Disease
Fundus Flavimaculatus
NH Drusen
Inflammatory
POHS
MF Choroiditis
Serpiginous Choroiditis
Toxoplasmosis
Toxocariasis
VKH
Rubella
Behcet's
SO
Neoplastic
Chroroidal Nevus
Choroidal hamngioma
Met. choroidal tumors
RPE hamartoma
Traumatic
Choroidal rupture
Intense Laser
Idiopathic




  • III. Retinal Physiology and Psychophysics


  • ERG
    • Mass response evoked from entire retina
    • Scotopic (rod response; dark-adapted)
      • Dim white flash below cone threshold ( rods = 1000x more sens. to light than cones)
      • Maximal combined response (dark-adapted)
      • Bright flash > max stimulation of rods and cones
    • Oscillatory potentials
      • Result of feedback interactions among integrative cells of proximal retina
    • Photopic (cone response; light-adapted)
      • 30 Hz flicker
      • cone response (8Hz = practical limit of rods)
  • Focal ERG
    • Dx organic dz in macula
  • Bright flash ERG
    • Ascertain retinal function in eyes w/ opaque media
  • Pattern ERG
    • Correlates w/ integrity of optic nerve
    • Info. about ganglion cells and their retinal interactions


    • a wave
      • negative wave; photoreceptor potential
    • b wave
      • positive wave; Muller & bipolar cells
      • oscillations in ascending b wave disappear in ischemia, CSNB
      • theoretically, ischemic retina would show increased b-wave implicit times and Log K
    • c wave
      • late +, correlated with RPE, EOG
      • hyperpolarization of apical RPE
    • x wave
      • bump on b wave in dark adap. bright flash = a wave


    • Diagnosis
      • infarcted retina would correlate with b/a wave amplitude ratio and Rmax
      • inversion of b/a ratio or delay in 30 Hz flicker response bodes poorly in CRVO
      • early siderosis has paradoxical larger ERG responses than normal, which in later stages become subnormal

  • EOG
    • Compares amplitude from dark and light adapted readings
    • Arden ratio = largest potential in light/largest potential in dark x 100 (normal > 1.85)
    • Useful in Best’s dz, hydroxychloroquine toxicity
  • VEP
    • N1P1N2P2 to confirm optic neuropathy, albinism
    • Also used for VA in children, malingering
  • Ultrasound (U/S)
    • PVD due to trauma/hemorrhage can be differentiated from RD by no attachments to optic nerve, irregular in thickness, cannot be traced to ora, and the amplitude is lower except when beam is perpendicular
    • New VH can be acoustically clear
    • asteroid is highly reflective, fills the vitreous which is usually retracted from retina
    • choroidal detachments are convex, rarely go posterior to vortex veins, and may be anterior to ora
    • metal/glass FB give shadowing, easier to see with lowering the gain
    • BB's give comet trail appearance

  • IV. Acquired Diseases Affecting the Macula


    • Central Serous Chorioretinopathy (CSCR)
      • Serous detachment of neurosensory retina due to altered barrier function and deficient pumping mechanism of RPE/CC
      • Usually affects healthy males 30-50 y.o.
      • Stress = possible etiologic factor
      • Symptoms: sudden blurred/dim vision, micropsia, and metamorphopsia, decreased color vision. May be assymptomatic.
      • FANG: focal hyperfluorescent leak from RPE in early phase that increases in size and intensity; “smokestack” in only 10%
      • Examine contralateral eye for RPE pigment alterations suggesting previous occurrences
      • 80% to 90% recover spontaneously in 1-6 mo.
      • 50% experience recurrences
      • laser Rx considered for:
        • persistence of serous detachment beyond 3-4 mo.
        • recurrence in eyes with visual deficit from prior CSCR
        • presence of permanent visual deficit from prior CSCR in fellow eye
        • development of chronic signs (cystic changes in neurosensory retina or widespread RPE abnormalities)
        • occupational or other pt. needs requiring prompt restoration of vision
      • Do NOT use steroids
    • Age-related Macular Degeneration (AMD)
      • Leading cause of severe central visual acuity loss in pts.>50 y.o. in U.S.
      • Severe visual loss is from CNV, geographic atrophy
      • Speculative risk factors: light pigmentation, sunlight exposure, smoking, hyperopia, HTN
      • Non-neovascular abnormalities in AMD:
        • Drusen:
          • dull yellow lesions in outer retina of posterior pole
        • abnormal thickening of inner aspect of Bruch’s MB
        • basal laminar deposits btw basal lamina of RPE and inner aspect of Bruch’s MB
        • basal linear deposits within inner aspects of Bruch’s MB
        • Pigment epithelial detachments (PED)
        • classification:
          • small (<64 um)
          • intermediate (64 – 125 um)
          • large (>125 um) *
          • hard
          • soft *
          • confluent *
          • calcific
          • * = more likely to progress to atrophy or CNV
        • RPE atrophy/attenuation
          • contiguous: geographic atrophy
          • noncontiguous/mottled depigmentation: nongeographic atrophy
        • Differential Dx (DDx)
          • CSCR
          • Pattern dystrophy
          • Drug toxicity (e.g. chloroquine)
      • Neovascular abnormalities in AMD:
        • Disruption in Bruch’s MB
        • Neovascularization from CC
        • New vessels accompanied by fibroblasts
        • Fibrovascular complex can destroy normal architecture of: CC, Bruch’s MB, RPE, photoreceptors, remaining outer retina


      • Classic CNV:
        • entire extent of CNVM can be identified in the FA early phase; often a lacy net or cartwheel of capillary vessels can be seen; mild leakage usu. seen in venous phase; dye progressively leaks and may collect in a pool of fluid in the subretinal space
      • Occult CNV:
        • entire extent of CNVM difficult to define on FA; may be areas of punctate areas of late hyperfluorescence which do not correspond to areas of drusen or RPE atrophy; hyperfluorescence and leakage may be partially blocked by serous detachment of RPE, subretinal blood, turbid fluid or pigment
      • Extrafoveal CNV:
        • >200 u from FAZ center
      • Juxtafoveal CNV:
        • 1-199 u from FAZ center
      • Subfoveal CNV:
        • involves FAZ center


      • Treatment
        • Laser Rx
        • Photodynamic Rx
        • Radiotherapy
        • Submacular surgery


    • Other causes of CNV
      • Ocular Histoplasmosis Syndrome (OHS)
        • Histoplasma capsulatum – fungus endemic to Mississippi and Ohio river valleys
        • 90% of pts. w/ typical fundus appearance have positive skin test
        • Fundus findings:
          • Small, atrophic, punched-out chorioretinal scars in midperiphery and posterior pole (histo spots)
          • Linear peripheral atrophic tracks
          • Peripapillary chorioretinal scarring
          • +/- CNV
          • NO vitreous inflammation (distinguishes OHS from multifocal choroiditis)


        • Macular Photocoagulation Study (MPS)
          • Eyes with OHS and extrafoveal CNV have cumulative risk of severe visual loss (SVL) (at least 6 lines of visual loss) of 44% at 5 years. Laser Rx of CNV reduced risk to 9%.
          • Rx also beneficial for juxtafoveal CNV. Initial VA 20/20 – 20/400. SVL = 25% without Rx vs. 5% w/ Rx at 3 yrs.
          • Subfoveal CNV: Rx not beneficial (unlike AMD).
        • Submacular surgery
      • Angioid streaks
        • Mnemonic: PEPSI (PXE, Ehlers-Danlos syndrome, Paget’s dz of bone, Sickle cell anemia (SS), idiopathic) 50% of pts. have no identifiable systemic dz
        • Breaks in thickened and calcified Bruch’s MB
        • FA: early window defect
        • almost always bilateral tapering a few mm from optic nerve
        • peau d'orange (macular pigment mottling) even without PXE
        • w/u: skin bx, alkaline phosphatase, Ca/Phos, sickle prep, 50% without systemic disease
        • CNV, exudative macular detachment

        • PXE
          • AR, present by age 30 y.o., F>M
          • abnormal elastic tissue leads to vascular fragility
          • GI bleeding, arterial insufficiency from calcification of vessels, HTN, ASHD
          • "plucked chicken" skin of neck, axilla, antecubital fossa, inguinal, and periumbilical areas
          • 80% have angioid streaks, punched out peripheral lesions, peau d'orange with severe LOV in 70%
          • angioid streaks due to abnormal elastic layer in Bruch’s MB
        • Paget's dz of bone
          • heavy calcified bones of pelvis, skull, femur, and humerus
          • excessive osteoclastic rxn. with secondary osteoblastic response
          • may have slow virus
          • increased serum alk. phosphatase, x rays, bone scan
        • Pathologic myopia
          • Spherical equivalent of –8.00 or greater
          • Axial length 32.5 mm or greater
          • Lacquer cracks
          • Fuchs’ spots (RPE hyperplasia - in response to small area of CNV that does not progress to significant disciform scar)
          • Posterior staphyloma
          • Elongation/atrophy of ciliary body
          • Atrophy of RPE and choroid
          • Cystoid, paving-stone, lattice degeneration
          • Peripheral thinning or hole formation
          • CNV
        • Familial drusen
          • (Doyne Honeycomb Dystrophy, Malattia Levantinese)
          • AD
          • Pigment clumping
          • Increased risk of CNV
          • ERG normal
          • EOG abnormal
  • V. Retinal Vascular Disease


    • Hypertensive Retinopathy

      • A/V changes: Gunn’s sign (nicking), Salus sign (90o crossing)
      • HTN also associated w/ BRAO, BRVO, CRVO, and retinal arterial macroaneurysms
      • Modified Scheie Classification
        • Grade 0 no changes
        • Grade 1 mild arterial narrowing
        • Grade 2 obvious arterial narrowing w/ focal irregularities
        • Grade 3 Grade 2 plus retinal hemorrhages and/or exudate
        • Grade 4 Grade 3 plus disc swelling
    • Hypertensive Choroidopathy
      • More common in younger patients w/ acute HTN (e.g. preeclampsia, eclampsia, pheochromocytoma, or accelerated HTN)
      • Elschnig spots
      • Siegrist streaks
    • Hypertensive Optic Neuropathy
      • Blurring of disc margin, flame hem., venous congestion, florid disc edema, secondary macular exudates
    • Diabetic Retinopathy
      • Epidemiology
        • Leading cause of blindness in U.S. in patients 20-64 y.o.
        • Duration of diabetes assoc. w/ increased prevalence of retinopathy both in pts. W/ NIDDM and IDDM
        • After 20 yrs. of diabetes, 99% of those w/ IDDM and 60% w/ NIDDM have some degree of retinopathy
      • Pathogenesis
        • EXACT cause of diabetic microvascular disease unknown
        • Commonly held that extended exposure to hyperglycemia>glycosylation of tissue proteins>vascular endothelial damage
        • In retinal vasculature: loss of pericytes>basement membrane thickening>capillary lumen compromise and decompensation of endothelial barrier function
      • Diabetes Control and Complications Trial (DCCT):
        • showed that intensive glycemic control assoc. w/ reduced risk of newly diagnosed retinopathy reduced progression of existing retinopathy in pts. w/ IDDM.
        • intensive glycemic control (compared to conventional Rx) assoc. w/ reduced progression to NPDR and PDR, reduced incidence of macular edema, and reduced need for PRP and focal Rx
      • Classification
        • Nonproliferative Diabetic Retinopathy (NPDR)
          • Microaneurysms (MA)
          • Dot and blot intraretinal hemorrhages (DBH)
          • Retinal edema
          • Hard exudates
          • Venous beading
          • Intraretinal microvascular anomalies (IRMA)
          • NFL infarcts (cotton wool spots)
          • Arteriolar abnormalities
          • Focal areas of capillary nonperfusion
          • vision loss in NPDR due to macular ischemia (capillary closure) and macular edema (increased intraretinal vascular permeability)
        • Severe NPDR
          • Characterized by any one of the following (ETDRS, 4:2:1 rule)
            • Diffuse intraretinal hemorrhages and MA in 4 quadrants
            • Venous beading in 2 quadrants
            • IRMA in 1 quadrant
        • Very severe NPDR
          • Any 2 of the above 3 characteristics
        • Proliferative diabetic retinopathy (PDR)
          • Extraretinal fibrovascular proliferation extends beyond the ILM
          • New vessels evolve in 3 stages:
            1. Fine new vessels w/ minimal fibrous tissue
            2. Increased size/extent of new vessels w/ increased fibrous component
            3. Regression of new vessels w/ residual fibrovascular proliferation along posterior hyaloid
        • Tractional complications
          • Partial PVD
          • Traction on NV
          • Preretinal or vitreous hemorrhage
          • Macular heterotopia
          • Retinal detachment (RD)
          • Retinal breaks
          • Rhegmatogenous RD
          • Chronic RD>further retinal ischemia>rubeosis>NVG
        • Clinical trials in diabetic retinopathy
          • Diabetic Retinopathy Study (DRS)
            • Randomized, prospective clinical trial evaluating panretinal photocoagulation Rx to one eye of pts. w/ clear media and advanced NPDR or PDR in both eyes
            • Primary outcome measurement was severe visual loss (SVL), defined as visual acuity less than 5/200 on 2 consecutive f/u visits 4 months apart
            • Demonstrated 50% or greater reduction in the rates of SVL in eyes Rx’d w/PRP vs. untreated control eyes during a f/u of up to 5 yrs.


            • High-risk PDR defined:
              • Mild NVD (1/4 to 1/3 disc area) w/ vitreous hemorrhage (VH)
              • Moderate to severe NVD w/ or w/o VH
              • Moderate (1/2 disc area) of neovascularization elsewhere (NVE) w/ VH
            • High-risk PDR also defined by 3 of the following 4:
              • Vitreous or preretinal hemorrhage
              • NV
              • NV on or near optic disc
              • Moderate to severe extent of NV


            • Complications of Argon laser PRP
              • Decreased visual acuity by 1 or more lines (11%)
              • Visual field loss (5%)
          • Early Treatment Diabetic Retinopathy Study (ETDRS)
            • Randomized, prospective study evaluating photocoagulation and aspirin Rx in pts. w/ less than high-risk PDR
            • Primary outcome measurement outcome was moderate visual loss (MVL) comparing baseline w/ f/u visual acuities. MVL defined as doubling of visual angle (e.g. a drop from 20/40 to 20/80), a drop of 15 or more letters on ETDRS vision charts, or a drop of 3 or more lines of Snellen equivalent


            • Clinically significant macular edema (CSME) defined as:
              1. Retinal edema at or within 500 u of the macular center
              2. Hard exudates at or within 500 u of the macular center if associated w/ adjacent retinal thickening
              3. Zone of retinal thickening larger than 1 disc area if located within 1 DD of the macular center


            • 3 central findings:
              1. Focal laser Rx for CSME resulted in a 50% or greater reduction in MVL
              2. PRP not recommended for mild or moderate NPDR, but is recommended for severe NPDR and should not be delayed when high-risk characteristics appear
              3. Aspirin (650 mg per day) did not alter the rates of progression of diabetic retinopathy, had no effect on visual acuity outcomes, and did not show any ocular benefits. i.e. no benefits/no contraindications
          • Diabetic Retinopathy Vitrectomy Study (DRVS)
            • Randomized, prospective clinical trial investigating the benefit of early (1-6 mos. After onset of VH) vs. late (at 1 year) for eyes w/ severe VH and visual loss (<5/200)
            • Outcome measurements: % of eyes w/ 10/20 or 10/50 visual acuity on standardized charts at 2 and 4 yr. f/u
            • Early vitrectomy was beneficial in Type 1 diabetics, but not in Type 2 or mixed diabetics
          • Diabetes Control and Complications Trial (DCCT)
            • Randomized, prospective clinical trial to study the connection between glycemic control and retinal, renal, and neurologic complications in Type 1 diabetics
            • Findings:
              • Intensive insulin therapy can delay the onset and slow the progression of diabetic retinopathy, nephropathy, and neuropathy in Type I diabetics
              • pts. w/ baseline mild or moderate NPDR showed worsening of retinopathy during first year.
              • Intensive control group had increased risk of hypoglycemic episodes and increased risk of weight gain
            • Not applicable to Type 2 diabetics or prepubescent pts.

          • Possible indications for pars plana vitrectomy (PPV) in diabetics
            • Dense, nonclearing VH
            • Tractional RD involving macula
            • Combined TRD and rhegmatogenous RD
            • Severe progressive fibrovascular proliferation (fp)
            • Anterior hyaloidal fp
            • Ghost cell glaucoma
            • Dense premacular hemorrhage
          • Laser Therapy
            • Laser Rx generally recommended for CSME and high-risk PDR
            • Risk factors for poor visual acuity despite laser Rx
              • Diffuse macular edema
              • Ischemic maculopathy
              • Hard exudates in fovea
              • Marked cystoid edema (CME)
            • Potential side effects of PRP
              • Decreased night vision, color vision, and/or peripheral vision
              • Loss of 1 to 2 lines of visual acuity
              • Loss of accommodation
              • Glare
              • Photopsia
              • Aggravation of macular edema
              • Choroidals
              • Mydriasis
              • VH
              • Retinal holes
              • RD
              • Lens and iris burns
              • ERM
              • foveal burn
            • Small spots cool quickly, large spots have high temps centrally
            • power density = power x time
            • media opacities
              • % increase in power needed
              • corneal 5-30% especially for stromal
              • flare/cell 10-35%
              • cataract 10-50%
              • vitreal 10-35%
            • Krypton
              • less scattering, less absorption by blood, yellow pigments (lens, foveal xanthophyll)
              • better uptake for choroidal tumors, blue iris
              • more choroidal uptake causes more pain, decrease accommodation, choroidal edema/hemorrhage
              • not good for acute hemorrhage during PRP, microaneurysms, blond fundi
              • really hits receptors, RPE, choroid
              • higher power needed for same lesions as argon
            • Rodenstock lens
              • minifies image, increases spot size
              • absorbs more energy than Goldman lens, so increase power
              • note: toward periphery, spots become smaller and relative power increases


    • Sickle Cell Retinopathy
      • Sickle trait (Hb AS) affects 8% of black Americans, 0.4% have sickle cell disease (Hb SS), 0.2% have hemoglobin SC disease
      • Sickle cell ocular anomalies are caused by intravascular sickling, hemolysis, hemostasis, and thrombosis
      • Initial event in pathogenesis of sickle cell retinopathy is peripheral arteriolar occlusion and capillary nonperfusion, which may lead to retinal neovascularization, usually at the border between perfused and nonperfused retina
      • Serious ocular complications more common w/ SC disease, while SS disease results in more systemic complications


      • Nonproliferative Sickle Cell Retinopathy
        • Salmon patch - intraretinal hem. after peripheral retinal arteriolar occlusion
        • Refractile spot – old resorbed hem. w/ hemosiderin deposition within retina just beneath ILM
        • Black sunburst – RPE hypertrophy, hyperplasia and pigment migration
      • Proliferative Sickle Cell Retinopathy (PSR)
        • Stage 1 – peripheral arteriolar occlusions
        • Stage 2 – peripheral A/V anastomoses
        • Stage 3 – sea fan neovascularization (60% autoinfarct)
        • Stage 4 – VH
        • Stage 5 – Tractional RD
      • Other ocular abnormalities in Sickle Cell Disease
        • conjunctival commas more common in SS disease, see after phenylephrine
        • disc sign of sickling – small vessels on optic disc can exhibit intravascular occlusions appearing as dark red spots
        • white without pressure, tortuous vessels, salmon patch hemorrhage
        • perifoveal depression (prior CWS infarct near macula)
        • can have perifoveal occlusion with decreased VA, CRAO
        • angioid streaks 5%, optic nerve comma, ischemic optic neuropathy
        • sea fans most common at 3 and 9 clock
      • Rx with scatter laser around fans with only few rows in normal retina


    • DDx of peripheral neovascularization
      • Vascular
        • Sickling hemaglobinopathies (SC, SS)
        • Other hemaglobinopathies (AC, AS)
        • Eales' disease
        • PDR
        • BRVO
        • BRAO
        • Talc retinopathy
        • ROP
        • FEVR
        • Hyperviscosity syndromes
        • Aortic arch syndromes/ ocular ischemic syndromes
        • CC fistula
        • MS
      • Inflammatory
        • Sarcoid
        • Uveitis, including pars planitis
        • Birdshot retinochoroidopathy
        • Toxoplasmosis
      • Misc.
        • Incontinentia pigmenti
        • Long-standing RD
        • Choroidal melanoma
        • Retinitis pigmentosa
        • Retinoshisis
    • ROP
      • See Pediatric Ophthalmology section


    • Vascular Occlusions
      • Branch Retinal Vein Occlusion (BRVO)
        • elderly, M=F, HTN, DM, arteriosclerosis, hyperopia, COAG
        • a/v crossing, wedge hemorrhage pattern, CWS, macular edema, dilated distal veins
        • if BRVO d/n occur at a/v crossing, consider inflammatory etiology
        • superotemporal quadrant (63%)
        • neovascularization in 22% of temporal BRVO
        • rubeosis in 1% of BRVO
        • Branch Retinal Vein Occlusion Study (BVOS)
          • 31% of eyes w/ >5 DD of nonperfusion develop NV
          • 12% of eyes w/ VH developed visual loss > 5 lines
          • 50-60% of pts 20/40 or better after 1 year
        • Laser Rx for macular edema (wait 3 mo. for maximum spontaneous resolution)
          • Rx’d eyes more likely to gain 2 lines of visual acuity (65%) vs. untreated eyes (37%)
          • Rx’d eyes more likely to have 20/40 or better at 3 yr. f/u (60%) vs. untreated (34%)
        • Scatter Rx for NV
          • Reduced risk of NV in eyes w/ 5 dd of nonperfusion from 22% to 12%; however, concluded that ischemia alone not indication for Rx
        • Wait for NV to develop, then Rx
        • In eyes w/ NV, reduced risk of VH from 60% to 30%
        • DDx
          • asymmetric DM
          • von Hippel’s disease
          • Coat's disease
          • parafoveal telangiectasia
          • ARMD
      • Central Retinal Vein Occlusion (CRVO)
        • Thrombosis of CRV at and post. to lamina cribrosa; atherosclerotic CRA impinges on CRV > turbulence > endothelial damage > thrombus
        • CRVO has two age peaks of 35 and 60 yrs. old, M>F, OS>OD, bilateral in 5%
        • transient visual obscurations, sudden loss of vision
        • initial VA has prognostic value, 1/2 have resolution and good final vision
        • commonly have cilioretinal artery occlusion as well
        • IOP decreased in affected eye
        • ischemic CVO increased in patients with APD, >10 CWS


        • Nonischemic CRVO
          • (aka partial, perfused, venous stasis retinopathy)
          • Mild dilation of CRV branches, dot/flame hem. in 4 quad., +/- macular edema, +/- disc edema
        • Ischemic CRVO
          • (aka nonperfused, complete, hemorrhagic)
          • More extensive 4 quad. Hem. and retinal edema, marked venous dilation, CWS
          • 10% achieve 20/400 or better
          • up to 60% w/ NVI in severe cases (usu. 3-4 mo. later)
        • Associations
          • COAG
          • HTN (61%)
          • DM (7%)
          • PVD
          • 3rd trimester
          • hyperviscosity
          • optic nerve tumors
          • optic nerve inflammation
          • anatomic abnormalities
          • Dysproteinemias, rarely Prot C and S deficiency
          • Oral contraceptives, diuretics
          • Sarcoid, Lupus
        • workup
          • CBC
          • ESR
          • Glucose
          • UPEP
          • lipid profile
          • bleeding time
          • CSR
          • HVF
          • fluorescein angiogram
          • IOP
          • carotid doppler
        • fluorescein angiogram
          • delay vein filling
          • ischemia >10 DD of nonperfusion
        • ERG
          • b/a <1 is evidence of ischemia
        • Rx
          • don't anticoagulant
          • Rx systemic dz
          • PRP for NVD/NVE/NVG
          • for macular edema, consider krypton, yellow

        • CVOS
          • multicenter, prospective, randomized clinical trial to evaluate CVO
          • NVI developed in 16% w/ 10-29 DA of nonperfusion, 36% w/ 30-74 DA, and 52% w/ 75 DA or more
          • PRP
            • prophylactic treatment in ischemic eyes did not significantly reduce iris neovascularization
            • prophylactic treatment seemed to blunt the response to PRP when neovascularization occurred
            • therefore, Do NOT PRP early
          • macular edema
            • no difference in vision between treated and nontreated eyes
      • BRAO
        • 80% with > 20/40, temporal vessels with Hollenhorst plaque at bifurcation
        • Associations (see CRAO)
        • Rx: digital pressure to dislodge embolus
        • 3 main types of emboli
          1. Cholesterol from carotid art. dz (Hollenhorst plaque)
          2. Platelet/fibrin from large vessel arteriosclerosis
          3. Calcific from cardiac valves
          • Rarely emboli from: cardiac myxoma, long-bone fracture (fat), infective endocarditis (septic emboli), IV drug abuse (talc)
      • CRAO
        • 2/3 of all artery occlusion, mid 60's, M>F, bilateral 2%
        • atherosclerosis-related thrombosis at level of lamina cribrosa
        • emboli seen in 20%
        • Painless loss of vision (PLOV) often during sleep, prior amaurosis
        • Irreversible damage to sensory retina after 90 min.
        • median survival is 5.5 yrs. (CV dz)
        • CF - LP VA, APD, cherry red spot in hours, gone in 1 month
        • thin vessels with boxcar blood, emboli in 20%
        • NVG in 2-25% in 1 month, retinal neovascularization rare
        • Associations
          • Embolic etiologies
          • TraumaCompression
          • Spasm of CRA
          • Coagulopathies
          • Drusen
          • Increased IOP
          • Temporal arteritis
          • OCP's
          • Migraine
          • Mucormycosis
          • HTN
          • DM
          • Cardiac disease
        • Workup: carotid doppler, cardiac echo, ESR, ANA, Hb electrophoresis
        • Rx
          • massage (15 sec firm with sudden release), paracentesis
          • Topical anti-glaucoma agents
          • IV Diamox, ?carbogen, ?hyperbaric O2
      • Ocular ischemic syndrome
        • 65 y.o., M>F, unilateral, 1:75,000, hard to diagnose
        • Due to severe, chronic carotid art obstruction
        • Atherosclerosis (AS) most common etio., but also: Eisenmenger syndrome, giant cell arteritis, other inflam. Dz
        • Symptoms: vision loss over weeks to months (20/40 to LP), orbital pain, prolonged visual recovery after bright exposure
        • Signs: NVI (2/3), A/C cells (1/5), retinal art. attenuation, dilated retinal veins, ret. hem., microan., NVD, NVE
          • Cataract
          • venous dilation
          • hemorrhage
          • Microaneurysms
          • CWS
          • NVD
          • Spontaneous pulse of CRA 5%
          • cherry red spot
          • emboli
          • Optic neuropathy
          • corneal striae
          • low grade iritis flare>cell
          • Low IOP even with NVI
          • NVI in 66%
        • w/u
          • carotid doppler and angiogram (consider MRA)
        • fluorescein angiogram
          • patchy choroidal filling, staining peripheral vessels
          • demarcated leading edge of filling, macular edema, microaneurysms
        • DDx
          • CRVO, DM (no hard exudates, unilateral)
        • Rx
          • 5 yr. mortality is 40%, often with DM, HTN, ASHD, CVA
          • PRP with NVI, transscleral YAG with endarterectomy
      • Ophthalmic artery occlusion
        • (probably 5% of CRAO's)
        • cherry red spot absent in 40%, NLP vision, IOP lower, AC rx
        • ERG flat, severe optic nerve atrophy, RPE mottling
      • Cilioretinal artery occlusion
        • isolated in 40%, good VA prognosis, 90% >20/40
        • with CRVO in 40%, nonischemic, 70% > 20/40
        • with AION in 20%, 20/400 to LP, r/o temporal arteritis.
      • Post ciliary artery occlusion
        • AION, small C/D <0.2, usually inferior disc edema

    • Cystoid macular edema (CME)
      • Intraretinal edema (Henle’s layer) in honey-comb cystoid spaces
      • Abnormal perifoveal retinal capillary permeability
      • +/- vitritis, +/- disc edema
      • High rate of spontaneous resolution
      • Rx: corticosteroids, prostaglandin inhibitors, CAI’s
      • associations
        • diabetic retinopathy
        • CRVO
        • BRVO
        • Uveitis
        • RP
      • post-surgical
        • Irvine-Gass syndrome (6-10 wks. post Sx)
        • Vitreous wick
    • Coats Disease (Retinal Telangiectasia)
      • Not hereditary, not assoc. w/ systemic vasculopathies, unilateral, M>F, 10-20 y.o.
      • lightbulb telangiectasia with lipid in both periphery and macula, massive RD is possible, capillary nonperfusion, leukocoria
      • abnormal vessels incompetent>deposition of serum and other blood components under retina
      • DDx
        • FEVR
        • Faciocapulohumeral MD
        • ROP
        • In milder cases consider: DR, BRVO, juxtafoveal RT, radiation retinopathy
      • Coat's-like response
        • massive perifoveal lipid in ARMD, BDR, RP, von Hippel’s disease, venous occlusion
      • Leber's miliary aneurysms
        • adult Coat’s, unilateral or bilateral, >40

    • Parafoveal (Juxtafoveal) Telangiectasia
      • not true telangiectasia, similar to diabetic microangiopathy w/ excess BM deposition in retinal capillaries
      • M>F, over 40, temporal telangiectasia
      • often with pigment, may have yellow foveal lesions, right angle venule, CNV, macular edema,
      • white dots, mild VA loss
      • 3 groups
        • group 1: (usu. males) unilat. parafoveal tel., congenital or acquired
        • group 2: (> 33% w/ abnormal glucose tol. test) bilat. parafoveal tel.
        • Group 3: bilat. perifoveal tel. w/ retinal capillary obliteration
      • Photocoagulation best for group 1
      • DDx:
        • BRVO
        • radiation
        • uveitis and macular edema
        • ARMD
        • DME
        • Macroaneurysm
    • HTN (66%), 60-70 y.o., F>M, serum lipid abnormal
      • usually within 3 bifurcations of disc, unilateral 90%, superotemp. artery
      • hemorrhage can be subretinal, intraretinal, preretinal or VH
      • rarely bleed more than once
      • decreased VA from edema, hemorrhage, Rx usually not needed
      • DDx: ARMD, melanoma (sub RPE blood), DM, venous occlusion


    • Phakomatoses (see also Pediatric Ophthalmology section)
      • Von Hippel-Lindau Disease (Angiomatosis Retinae)
        • AD (20%), hereditary and sporadic forms, bilateral (50%), capillary hemangiomas (the size of microaneurysms early on) presenting in 20 y.o. - 30 y.o.
        • Lindau has CNS tumors, cysts of viscera, malig. hypernephroma, pheochromocytoma, meningioma, renal cell CA
        • Leading causes of death: cerebellar hemangioblastoma, renal cell CA
        • midperipheral tumor, tortuous feeder arteriole, engorged draining venule, macular lipid, exudative RD
        • can look like Coat’s
        • laser or cryo tumors
        • whole body CT q2yrs
      • Sturge-Weber Syndrome (encephalofacial angiomatosis)
        • Facial cutaneous angioma (nevus flammeus, port-wine stain)
        • Ipsi. leptomeningeal vasc. malformation > cerebral calcification
        • Jacksonian seizures (focal > grand mal)
        • Focal neuro deficits (hemianopia, hemiparesis, etc. )
        • Highly variable mental deficiency (may be normal)
        • NOT GENETICALLY TRANSMITTED, BUT LESIONS PRESENT AT BIRTH
        • Railroad track sign (curvilinear calcium deposits paralleling cerebral convolutions)
        • Tomato catsup fundus (increased # of well-formed choroidal vessels)
        • Choroidal hemangiomas/choroidal exudation/ possible RD
        • Laser tx of circumscribed hemangiomas may be effective
        • Glaucoma (33%) assoc. when nevus flammeus affects upper lid
        • Corneal enlargement at birth (66%)
      • Congenital Retinal AV Malformation (Wyburn-Mason Syndrome, racemose angioma)
        • Unilateral, nonhereditary
        • Lesions located in retina or optic nerve
        • No leakage on FA
        • W-M syndrome: ipsilateral vascular malformations in brain, orbit, face
        • Vascular tortuosity
      • Retinal Cavernous hemangioma
        • AD or sporadic
        • grape clusters
        • FA: slow filling, no leakage
        • VH possible due to traction
        • no Rx usually, can have intracranial lesions
      • Eales' (primary idiopathic retinal vasculitis)
        • Obliterative vasculitis of peripheral retina, usu. bilateral
        • Indians, 20-30 y.o., healthy, M>F, ?association with TB hypersensitivity
        • peripheral nonperfusion, NV, hemorrhage, sheathing, anterior chamber and vitreal cells, macular edema
        • NVD/NVE in 80% with fibrous component, TRD, VH
        • RX light scatter in nonperfused area, most retain >20/40
        • Possible causes:
          • Cardiac valvular dz
          • Cardiac arrhythmias
          • Ulcerated atheromatous dz of carotids
      • Hemoglobinopathies
        • Misc. Vascular
          • Situs Inversus
            • bilateral in 80%, often in tilted discs

          • Congenital Tortuosity
            • usually arterial, may be AD, associated hyperopia
            • consider Tetralogy of Fallot, heart defects

      • CWS
        • In DM usually resolve 5-7 wks., <1/4 dd
        • Causes
          • HTN
          • Collagen vascular disease
          • AIDS
          • Leukemia
          • Heart valve disease
          • Purtscher's retinopathy
          • Radiation
          • Partial CRAO
          • venous obstruction
          • Metastasis
          • Anemia
          • sepsis
          • High altitude
          • Papilledema/papillitis
          • pancreatitis
          • IVDA
          • DM
        • DDx
          • Myelinated NFL, Choroiditis, subretinal fibrosis, Histo spot, Lipid, candida
      • Optociliary shunts
        • DDx
          • Prepapillary vascular loop, NVD, Splinter hem., Wyburn Mason syndrome
          • Causes
            • CRVO, Optic nerve meningiomas, gliomas, Arachnoid cysts, chronic papilledema, Phakomatoses, Possibly COAG, high myopia, Sub ILM hemorrhages
    • Valsalva retinopathy, macroaneurysm, and PDR can all have sudden subhyaloid or sub-internal limiting membrane bleeding
      • Standard therapy is to observe and then treat with vitrectomy
      • Nd:YAG membranotomy using fundus laser lens has been reported with more rapid clearing of hemorrhage
        • 1-3 openings inferiorly using from 10-150 bursts with 8-12 mJ in fundamental mode
      • Blood usually clears within one week

  • VI. Congenital and Stationary Retinal Disease


    • Color vision (cone) abnormalities
      • Abnormality or loss of red-sensitive cone pigment = protan, green = deutan, blue = tritan
      • Dichromat – abnormal individual requiring 2 of 3 colors
      • Anomalous trichromat – requires 3 colors but in abnormal proportions
      • Trichromat – requires all 3 primary colors of light (RGB) to match an arbitrary color
      • Congenital
        • XLR
        • Red-green abnormalities
        • 8% of males, 0.5% of females
        • bilateral, stable
        • don’t misname colors; confuse reds, browns, olives, golds, pastels
      • Acquired
        • Blue-yellow abnormalities
        • M=F
        • Unilateral, can progress
        • Incorrect naming of colors
      • Achromatopsia
        • Absence of color discrimination
        • Congenital nystagmus, poor visual acuity, photoaversion
        • ERG: absence of conventional cone responses, rod response rel. normal, no cone plateau on dark adaptation
      • Blue-cone monochromat
        • XLR
        • May be clinically indistinguishable from rod monochromat
        • Have only blue sensitive cones
        • Caused by loss of function of both red and green cone pigment genes on X chromosome
        • 20/40 – 20/200 vision
      • Rod monochromat (true color blindness)
        • AR
        • No cone function
        • See world in shades of gray
        • 20/40 – 20/200 vision
      • Night vision (rod) abnormalities
        • normal fundus
        • CSNB
        • Bipolar cell layer defect
        • Life-long stable abnormal scotopic vision
        • Vision: normal to 20/200
        • Significant myopia
        • ERG: negative ERG (Schubert-Bornschein form) maximal DA response, large a-wave w/ absent or reduced b-wave; also reduction of both scotopic a- and b-waves (rarer)
        • (3 subtypes)
          • XL (most common)
          • AD
          • AR
      • abnormal fundus
        • Fundus albipunctatus
          • Recovery of normal rhodopsin levels after intense light exposure may take several hours
          • Rod ERG = minimal, recovery w/ DA
          • Visual acuity and color vision slightly subnormal
          • Fundus: multiple yellow-white dots in posterior pole (excluding fovea) radiating to periphery
        • Retinitis punctata albescens
          • Variant of RP
          • Fundus: yellow-white dots w/ vessel attenuation
          • Severely depressed ERG that d/n recover w/ DA
        • Fleck retina of Kandori
          • Larger patch-like flecks
          • Less severe night vision impairment
        • Oguchi disease
          • Very slow DA
          • Normal rhodopsin regeneration
          • Fundus: yellow iridescent sheen after light exposure that disappears after DA (Mizuo-Nakamura phenomenon)
      • Progressive night blindness
        • DDx
Goldman Favre
RP
Chorioderemia
gyrate atrophy
Difuse choroidal atrophy



VII. Hereditary Retinal and Choroidal Dystrophies



  • Usually bilateral symmetric disease with insidious onset without FH
  • Dx for prognosis and genetic counseling
  • Most are AD except Stargardt's and myopia (AR), Juvenile retinoschisis (XL)
  • Diffuse Photoreceptor Dystrophies
    • Rod-Cone Dystrophies (Retinitis Pigmentosa)
      • Poor night vision, constricted VF, bone spiculization of the fundus, ERG evidence of photoreceptor cell dysfunction
      • AD (least severe), AR (most common), XLR (rare and most severe)
      • Affects 1 in 4000 in U.S.
      • 20% = AD, <10% XL, remainder = AR or isolated simplex
      • Fundus: bone spiculization, arteriolar attenuation, waxy pallor of optic disc, CME, vit. cells
      • PSC
      • Many pts legally blind by VF (< 20o of central field to III4e in many states)
      • ERG: loss or marked reduction of rod and cone signals (rod loss predominates), a- and b-waves reduced; carrier state of XLR shows mild reduction or delay in b-wave response
      • R/O acquired causes of retinal degeneration that can mimic RP: old ophthalmic or choroidal artery occlusion, diffuse uveitis, infections such as syphilis, retinotoxic drugs, systemic metabolic dz (Refsum’s dz, abetalipoproteinemia); unilateral dz that can also mimic RP: prior RD, DUSN, retained IOFB
      • No Rx, but genetic counseling important
      • Many Classifications e.g.
        • TI
          • diffuse pigmentary changes, concentric VF loss, ERG flat,
          • early nyctalopia, 10-20 y.o.
        • TII
          • regional, usually inferior, 20-30 y.o. nyctalopia, may never get it
          • ERG worse than expected from fundus,
          • 90% with 20/40 at age 50, sector VF dropout
        • TIII
          • as above but with better ERG than expected, even better prognosis
        • TIV
          • pericentral pigment just beyond arcades
          • best prognosis, rarest, ERG normal, nyctalopia
      • Secondary RP

        • myotonic dystrophy, Paget's disease, T1 DM, optic nerve pallor, Refsum's disease, Friedrich's ataxia, Battan's, Charcot-Marie tooth, Alstrom’s dz, Cystinosis, Waardenburg syndrome, Stickler's, PXE, CPEO, Incontinenti pigmenti, MPS I, II, III, Homocystinuria, Bardet-Biedl
      • Bardet-Biedl Syndrome
        • AR
        • RP plus: Obesity, polydactyly, hypogonadism, MR
      • Usher Syndrome
        • RP plus hearing loss, 10% of all RP, AR, 3:100,000, carrier 1/100
        • TI has profound sensorineural hearing loss, unintelligible speech, absent vestibular function
        • TII has good speech, variable ERG, normal vestibular sensitivity, no ataxia, mental retardation, psychosis
        • DDx: Alstrom syndrome, Bardet Biedl syndrome, retinal-renal syndromes, Refsum’s dz, Leber’s CA, mitochondrial myopathies, congenital rubella, MPS
      • Deafness + RP
        • Alport's
        • Alstrom's
        • Cockayne's
        • Friedrich's ataxia
        • MPS I
        • Osteopetrosis
        • Refsum's
        • Waardenberg
      • PseudoRP
        • Rubella
        • Childhood exanthemlues
        • VKH
        • Toxemia of pregnancy
        • 4-amino quinolone
        • Phenothiazines
        • CRAO
        • Stargardt's
        • Trauma


      • Cone Dystrophy
        • Heterogeneous group of dz
        • Progressive central visual acuity loss (HM late), better vision at night
        • Poor color discrimination
        • Photoaversion
        • May have nystagmus
        • May have symmetrical bull’s eye pattern of macular atrophy
        • optic nerve pallor, vessel attenuation
        • photopic ERG absent, scotopic normal
        • can look like RP at endstage
    • Cone-Rod Dystrophy
      • Rod dysfxn in addition to cone dysfxn
      • Constricted VF, ring scotomata
      • Peripheral bone spiculization
      • Nyctalopia w/ poor visual acuity and poor color recognition
    • Macular and RPE Dystrophies
      • Stargardt's Disease (posterior pole) (Fundus Flavimaculatus if flecks diffuse)
      • AR (some AD)
      • juvenile, normal macula early to beaten bronze look, prog. loss of VA 20/50 to 20/200
      • ERG mimics rod-cone dystrophy
      • EOG normal
      • FA - dark choroid (blockage of choroidal fluorescence by RPE pigment)
      • flecks secondary to lipofuscin
      • early loss of reflex, if long standing, salt-pepper retina
      • mild red green loss, flecks come and go, macular involvement may take 6-20 yrs.
      • DDx: cone dystrophy, ceroid lipofuscinosis, pattern dystrophy
      • DDx of flecks

        • Retinitis punctata albescens
          • prog. VF loss, nyctalopia, vascular attenuation, dots in retina can be pigmented, AR
        • Fundus albipunctatus
          • CSNB, nyctalopia, VA, VF stay normal, dots can increase/decrease, AR, AD
          • regeneration of ERG scotopic waveforms highly characteristic

        • Kandori fleck retina
        • PXE
        • ARMD with cholesterol
        • crystalline retinopathy
        • Aicardi's
        • XL albinism carrier
        • POHS
        • Birdshot
        • RP
        • Talc
        • Oxalosis
        • Methoxyflurane anesthesia
        • Central areolar choroidal dystrophy
          • 30's, VA 20/30 - 20/100, foveal granularity, AD/AR, ERG/EOG may be normal
        • North Carolina dystrophy
          • AD w/ complete penetrance
          • Variable phenotype
          • Drusen-like changes
          • Disciform lesions w/ CNV
        • Macular staphylomata
          • ERG, EOG, color vision: all normal
          • Progressive loss of central vision, reaching maximal severity in teens
        • Best Disease
          • AD
          • Mutation mapped to long arm Chrom. 11
          • Early “egg-yolk” macular lesion
          • 3 -15 y.o., variable penetrance, 20/30-20/50 for yrs. even with macular lesion
          • lesion: usually 1DD with lipofuscin at RPE level, can be multiple
          • decreased EOG (Arden ratio < 1.5)
          • FA blockage
          • ERG normal

        • Foveomacular dystrophy (adult Best's)
          • 40-60 y.o.
          • 1/3 DD lesion with central pigment
          • ring of hyperfluorescence surrounds blockage
          • PAS+, paracentral drusen, slow visual loss, usually maintain reading VA for life
          • EOG: normal or minimally reduced
          • ERG normal

        • Diffuse Drusen (Dominant Drusen, Doyne’s Honeycomb Dystrophy)
          • < 50 y.o.
          • diffuse drusen extending beyond arcades esp. nasal to disc
          • good central vision barring extensive involvement
          • may degenerate into vitelliform cyst

        • Pattern Dystrophies
          • Good vision in first 5 decades of life
          • Relatively good prognosis, except risk of atrophic maculopathy
          • Pattern of granular or reticular black pigmentation at level of RPE
          • No drusen or yellow flecks
          • EOG: borderline or mildly reduced


          • Sjogren reticular dystrophy
            • AR
            • Network of pigmented lines surrounding macula and extending to periphery
          • Butterfly dystrophy
            • AD
            • Pigment deposits radiate from fovea in butterfly pattern

      • Choroidal Dystrophies

      • =

        • Diffuse degenerations

=

          • Choroideremia
            • XLR
            • scalloped RPE and loss of choroid, CC, and RPE starting at equator and moving anterior/posterior
            • nyctalopia, 4-20 y.o., VF loss peripheral, no spicules but clumping
            • < 20/200 by 50 y.o.
            • ERG abnormal
            • FA characteristic
            • Carriers: can have symptoms, pigment clumping, RPE granularity, ERG and VF normal
            • Abnormal gene codes for a component of rab geranylgeranyl transferase
            • DDx: high myopia, gyrate atrophy, RP, Bietti’s crystalline dystrophy
          • Gyrate atrophy
            • AR
            • ornithine aminotransferase def., 10X increased ornithine, as early as 8 y.o.
            • scalloped RPE/CC loss, peripheral paving stone, rest of RPE increased pigmentation, myopia, cataracts
            • progressive loss of VA and VF , nyctalopia, abnormal EEG, changes in hair/muscle fibers, ERG abnormal
            • <20/200 by 40 y.o.
            • dietary restriction of arginine, vit. B6

      • Regional and Central Choroidal Dystrophies
          • Demarcated atrophy of CC and RPE in macula w/ normal full field ERG and EOG
          • VA 20/20-20/200
          • Central areolar choroidal dystrophy
          • Central areolar pigment epithelial dystrophy
          • North Carolina dystrophy
            • AD
            • Early onset
            • Staphylomatous macular lesion stable by 10 y.o.
            • Long arm Ch 6

      • Other Maculopathies
        • Sorsby macular dystrophy
          • Bilateral CNV by 40 y.o.
          • Central geographic atrophy w/ black pigmentation
          • Gene defect: codes for tissue inhibitor of metalloproteinase
      • Inner Retinal and Vitreoretinal Dystrophies
        • Juvenile retinoschisis
          • XLR
          • VA: 20/20 to LP
          • Splitting in NFL (unlike senile form: OPL,ONL)
          • Primary abnormality in Muller cells
          • strabismus, nystagmus, poor VA 20/60, progressive, VH from schisis vessels
          • foveal schisis (cartwheel) since birth in 1/2, peripheral NFL schisis over time
          • round parafoveal microcysts (use red free, slit),
          • perivascular cuffs, vitreous veils, optic nerve edema
          • dark adapt normal
          • ERG decreased b-wave reflects panretinal nature of dz and schisis btw inner and outer retina
          • EOG normal, XLR
        • Goldmann-Favre Syndrome
          • Retinoschisis, RP, vitreal degeneration
          • Nyctalopia
          • ERG: abnormal cone response w/ absent rod fxn (may be flat)
          • VF loss

VIII. Selected Retinal Degenerations Associated w/ Systemic Disease


  • Friedreich’s ataxia

    • AR
    • Spinocerebellar degeneration
    • Limb incoordination
    • Nerve deafness
    • Retinal degeneration
    • Optic atrophy
  • Myotonic dystrophy (Steinert’s dz)

    • AD
    • Muscle wasting
    • Christmas tree cataract
    • Retinal degeneration, +/- pigment deposits
    • Subnormal ERG
    • Normal EOG
    • Southern blot: repeated trinucleotide on Chrom 19
  • Duchenne Muscular Dystrophy

    • ERG: negative waveform (similar to CSNB) normal a-wave, reduced b-wave
    • Do not have night blindness
    • Mutation in gene for dystrophin
  • Retinal-renal dysplasia

    • AR
    • Juvenile-onset renal failure
    • Pigmentary retinopathy
  • Alport syndrome

    • AD
    • Nephropathy
    • Deafness
    • Myopia
    • Cataract
    • RD
  • Alstrom syndrome

    • AR
    • Pigmentary retinopathy
    • Diabetes
    • Obesity
    • Deafness
    • Normal mental capacity
  • Gardner syndrome (familial adenomatous polyposis)

    • Lesions sim. to CHRPE but smaller, bilateral, more variegated
  • Incontinentia pigmenti

    • XLR, yet primarily affects females since males rarely survive
    • Skin pigmentation (lines, whorls)
    • Alopecia
    • Dental anomalies
    • Optic atrophy
    • Cataract
    • Nystagmus
    • Pigmentary retinopathy
    • Conjunctival pigmentation

  • Cancer-Associated Retinopathy

    • gradual nyctalopia with progressive retinal degeneration leading to a flat ERG
    • may be symptomatic before primary tumor is found
    • associated with poor prognosis in cases of lung tumors (esp. small cell CA)
    • probably from immune responses to antigens common to retinal and tumor cells (for example, a photoreceptor protein recoverin)
    • Rapid, progressive loss of vision (central and peripheral)
    • Vision loss may precede clinical recognition of tumor
    • Arterial narrowing in fundus
    • VF: ring scotoma
    • High titre of 23 kD Ab specific for pro. sim. to recoverin
    • any late-onset rapidly progressing retinal dysfunction should raise suspicion of occult malignancy
  • Malignant melanoma

    • ERG: sim. to negative ERG of CSNB (preserved a-wave, loss of rod b-wave and the on-pathway responses of cones)
    • photopsia
  • Metabolic Defects

    • Albinism
      • 2 clinical patterns; both may have photophobia, iris transillumination, hypopigmented fundi
      • True albinism:
        • hypoplastic fovea, no foveal pit, no yellow macula lutea pigment; may also have abnormal retinogeniculostriate projections (temporal fibers may decussate) perhaps accounting for high rate of strabismus
      • Oculocutaneous albinism (eyes and skin affected)
        • Reduction in amount of primary melanin in melanosomes
        • AR
        • Tyrosinase positive (some degree of pigmentation)
        • Tyrosinase negative (total lack of pigment)
      • Ocular albinism (only eyes affected)
        • Reduction in number of melanosomes
        • XL
      • 2 potentially lethal forms of albinism:
        • Chediak-Higashi syndrome
          • Oculocutaneous albinism w/ extreme susceptibility to infxn.
        • Hermansky-Pudlak syndrome
          • Oculocutaneous albinism w/ platelet defect
          • Easy bleeding/bruising
          • Usu. Puerto Rican
      • albinoidism
        • Neuronal ceroid lipofuscinosis (several types)
          • Haltia-Santavuori (infantile form) 8 – 18 mo.
          • Jansky-Bielschowsky (late infantile from) 2 – 4 y.o.
          • Vogt-Spielmeyer-Batten (juvenile form) 4 – 8 y.o.
          • Kufs (adult form)
          • Infantile forms: optic atrophy, macular pigment changes, peripheral mottling, low or absent ERG, low VEP, cataracts
          • Late infantile and juvenile forms: macular granularity/bull’s eye lesion, optic atrophy, retinal vessel attenuation
          • Adult form: no ocular findings

    • Abetalipoproteinemia
      • AR
      • Fat malabsorption, fat-soluble vitamin def.
      • Pigmentary retinopathy
      • Spinocerebellar degeneration

    • Refsum dz (phytanic acid storage dz)
      • Cerebellar ataxia
      • Polyneuropathy
      • Pigmentary retinopathy
      • Anosmia
      • Deafness
      • Ichthyosis
      • Cardiac myopathy/arrhythmias

    • Peroxisomal disorders
      • Zellweger syndrome
      • Infantile retinal degeneration
      • Hypotonia
      • Psychomotor retardation
      • Seizures
      • Characteristic facies
      • Renal cortical cysts
      • Hepatic interstitial fibrosis
      • Death usu. in infancy

    • Mucopolysaccharidoses (MPS)
      • Caused by inherited defects in catabolic lysosomal exoenzymes that degrade the acid mucopolysaccharides – dermatan sulfate, keratan sulfate, and heparan sulfate
      • All are AR except type II (Hunter) is XLR
      • Only those MPS in which heparan sulfate is stored are associated w/ retinal dystrophy
      • I-H (Hurler)
      • I-S (Scheie)
      • II (Hunter)
      • III (Sanfilippo)


    • Other lysosomal metabolic disorders
      • Tay-Sachs dz (GM2 gangliosidosis type I)
        • Deficient subunit of hexosaminidase A
        • Glycolipid deposition in retina, brain > blindness, MR
      • Cherry red spot
      • Sandhoff dz (GM2 gangliosidosis type II)
      • Gaucher dz (nonneuropathic adult form)
      • Niemann-Pick dz (type A)
      • Mucolipidosis I
      • Cherry-red-spot-myoclonus syndrome
      • Goldberg-Cotlier syndrome
    • Fabry disease
      • XL
      • Ceramide trihexoside accumulates in smooth muscle of blood vessels in the kidneys, skin, GI tract, CNS, heart, reticuloendothelial system
      • Ocular signs: corneal whorls (verticillata), tortuous retinal and conjunctival vessels, cataract

    • Amino acid disorders
      • Cystinosis
        • 3 types: nephropathic, late-onset (intermediate), benign
        • cystine crystals accumulate in cornea and conj.
        • Retinopathy only in nephropathic type
        • Onset 8-15 mo.
        • Renal failure
        • Growth retardation
        • Renal rickets
        • Hypothyroidism
        • Rx w/cysteamine
    • Mitochondrial DNA disorders
      • Kearns-Sayre syndrome
        • CPEO
        • Pigmentary retinopathy
        • Cardiomyopathy
      • NARP syndrome
        • Neurogenic muscle weakness, ataxia, RP

    • DIC
      • associated with serous RD
    • Lupus anticoagulant
      • with venous/arterial occlusion, amaurosis, diplopia, neovascularization with VH, and VF loss
    • Prot C/S def
      • with occlusion, amaurosis, VH/RD in neonates
    • ITP
      • with retinal hemorrhage, Grave's disease, take good drug hx
    • TTP
      • with papilledema, EOM palsies, VF defects, retinal hemorrhage, occlusion, and serous RD
    • Thrombocytopenia
      • with retinal hemorrhage, VH especially with anemia
    • Hodgkin's Lymphoma
      • with periphlebitis, vitritis, CR, serous RD, CWS, optic nerve edema
    • Dysprotenemias
      • Multiple Myeloma
        • with stromal crystals, pars plana cysts, microaneurysms, NFL hemorrhage, serous RD
        • orbital mass effect by plasmocytoma, rx with radiation
        • ciliary body cysts in 1/3
        • optic nerve swelling, CN VI palsy
      • Waldenstrom's macroglobinemia
        • up to 50% with hyperviscosity retinopathy, serous RD
        • may mimic CRVO
    • Leukemia
      • hyperviscosity signs, preretinal white infiltrates (3%), CWS, CRVO, peripheral neovascularization and microaneurysms, subconjunctival hemorrhage
      • retinal hemorrhage (1/3) is striking, often in posterior pole and any level
        • no prognostic value
      • Roth spots
        • are not pathognomonic for SBE
      • DDx
        • Birth trauma,battered children,prolonged or difficult intubation, Intracranial bleed (AVM), anemia, anoxia, CO poisoning, capillary fragility (HTN, DM)
    • Pregnancy
      • increased IOP last 1/2, CE with variable refractive changes
      • CSR, ptosis, CC fistula
      • toxemia with serous RD, HTN changes
      • increased PDR, BDR
    • Hyperviscosity syndrome
      • signs
        • bleeding diathesis
        • gums and mucosa, nose, increased bruising
      • ophthalmic problems
        • altered vision, diplopia, and vascular tortuosity
        • hemorrhages can be dot/blot, flame shaped, large or small, with or without white centers
        • can have orbital soft tumors
      • neurologic findings
        • headache, vertigo, ataxia, and seizures
      • systemic
        • malaise, anorexia, weight loss, CHF, and renal insufficiency
      • differential includes bilateral mild CRVO, which usually has more hemorrhage and less venous dilatation
    • Waldenstrom's macroglobulinemia
      • increased IgM, tight tortuous vessels
      • up to 50% of patients have retinal findings
    • Multiple Myeloma
      • pars plana cysts difficult to appreciate clinically
      • uncommonly crystalline corneal deposits, central Descemet copper deposit

IX. Peripheral Retinal Abnormalities


  • Landmarks

    • Long posterior ciliary nerves at 3:00 and 9:00
    • Short posterior nerves usu. superior and inferior
    • Vortex veins at the equator
  • Scleral depression

    • Depress just posterior to recti insertions, since ora serrata lies just underneath Spiral of Tillaux
  • Retinal breaks - Any full-thickness defect in the neurosensory retina

    • Horseshoe (flap) tear
      • Strip of retina pulled anteriorly by vitreoretinal traction
    • Giant retinal tear
      • Tear that extends 90o or more circumferentially
    • Operculated hole
      • Traction is sufficient to tear a piece of retina completely free from adjacent retinal surface
    • Retinal dialysis
      • Break occurring along ora serrata, commonly resulting from blunt trauma (superotemporal quadrant most common if traumatic)
      • Usu. at posterior border of vitreous base
    • Atrophic retinal holes
  • Posterior vitreous detachment (PVD)

    • Vitreous gel most firmly attached at vitreous base
      • Vitreous base (VB) – circumferential zone straddling ora serrata, extending 2mm anterior and 4mm posterior to ora
    • At VB, vitreous collagen fibers firmly attached to BM of retina and pars plana epithelium; separation here easily causes tears
    • Vitreous also firmly attached at:
      • Optic disc margin
      • Macula
      • Major retinal vessels
      • Margin of lattice degeneration
      • Sites of chorioretinal scars
    • Most retinal tears result from spontaneous or traumatic PVD
    • Initial event – syneresis (liquifaction) of central vitreous
    • Hole develops in posterior vitreous
    • Liquified vitreous passes into subhyaloid space, rapidly separating posterior hyaloid from retina
    • Vitreous gel remains attached at VB
    • Resulting vitreous traction, commonly at posterior margin of VB, may produce retinal break
    • symptoms: photopsia, floaters (VH, glial cells from optic disc, aggregated collagen fibers)
    • 15% of pts w/ acute, symptomatic PVD have a retinal tear
    • 70% of pts w/ VH assoc. w/ PVD have a retinal tear
    • 2 to 4% of pts w/o VH assoc. w/ PVD have a retinal tear
    • Prevalence of PVD increases w/:
      • Increased axial length
      • Advanced age
      • Aphakia
      • Inflammatory dz
      • Trauma
      • myopia
  • Traumatic retinal breaks

    • Traumatic breaks often multiple and commonly found inferotemporal and superonasal
    • Dialysis most common, usu. at posterior border of VB
    • Avulsion of VB (anterior vitreous detachment) may be assoc. w/ a dialysis, and is considered pathognomonic of ocular contusion. “Buckle handle”
    • Vitreous may eventually liquify over a tear, subsequently leading to RRD. Clinical presentation of RD usu. delayed
    • 12% immediately
    • 30% in 1 month
    • 50% in 8 months
    • 80% in 24 months
    • traumatic RD in young pts. usu. show chronicity
    • shallow w/ multiple demarcation lines
    • subretinal deposits
    • intraretinal cysts
    • Blunt trauma (A/P compression w/ equatorial expansion)
      • Coup mechanism (adjacent to point of trauma)
      • Contrecoup injury (opposite point of trauma)
  • Lesions predisposing to RD

    • Lattice degeneration

      • Found in 6% to 10% of general population
      • Bilateral in 1/3 to 1/2
      • More common in myopes
      • Histopathology: discontinuity of ILM, overlying pocket of liquified vitreous, condensation and adherence of vitreous at lesion margin, atrophy of retinal inner layers, sclerotic blood vessels
      • Underlying cause in 20% to 30% of all RRD
      • Progresses to RD by 1) tractional tear at lateral or posterior margin 2) atrophic hole within lattice
    • Vitreoretinal tufts

      • Small, peripheral retinal elevations caused by focal areas of vitreous or zonular traction
      • Classified as: noncystic retinal tuft, cystic retinal tuft, zonular-traction retinal tuft
      • Cystic and zonular-traction types more likely to predispose to RD because of firm vitreoretinal adhesions
    • Meridional folds

      • Folds of redundant retina
      • Usu. superonasal
      • Most commonly assoc. w/ dentate processes
    • Enclosed ora bays

      • Oval islands of pars plana epithelium located just posterior to ora; completely (or almost completely) circumscribed by peripheral retina
      • Peripheral retinal excavations
      • May represent atypical lattice
      • Often aligned w/ meridional folds
  • Lesions not predisposing to RD

    • Cobblestone (paving stone) degeneration

      • Small, discrete areas of ischemic atrophy of outer retina
      • Attenuation or absence of CC
      • Loss of RPE and outer retinal layers
      • Adhesion btw remaining retinal layers and Bruch’s MB
      • Most common in inferior quadrants, anterior to EQ
      • Appear yellow-white, may be surrounded by rim of hypertrophic RPE
      • Large choroidal vessels may be visible (RPE absent)
      • May be confluent
      • Present in 22% of people >20 y.o.
    • RPE hyperplasia

      • Stimulated by chronic low grade traction
      • May straddle ora
      • Trauma
      • inflammation
    • RPE hypertrophy

      • Large cells w/ large melanin granules
      • Usu. just posterior to ora
      • Similar histopath. to CHRPE
    • Retinal Breaks

      • 6% of all eyes have a retinal break, but only 1 person per 10,000 – 15,000 develops an RD; given an avg. life expectancy of 74 yrs., 0.07% of the population will develop an RD during their lifetime
      • acute breaks (usu. assoc. w/ VH or heme at tear margin) are more dangerous than old breaks
      • tears such as round, atrophic holes, operculated holes, macular holes have a minimal chance of progressing to RD
      • acute, symptomatic tears carry a considerable risk
      • factors to consider in risk/benefit of Rx: symptoms, residual traction, location of break, phakic status, refractive error, status of fellow eye, family history, presence of subretinal fluid, and follow-up reliability

  • Retinal Detachment

    • Rhegmatogenous Retinal Detachment (RRD)

      • Most common type of RD
      • Rhegma: Greek for break
      • Caused by liquified vitreous passing through retinal break into potential space between sensory retina and RPE
      • Definite break found in 97% of RRD’s
      • 50% of pts. w/ RRD have photopsias and floaters
      • IOP usu. lower in affected eye
      • Shafer’s sign: small clumps of pigmented cells (tobacco dust) in vitreous or AC
      • Corrugated appearance, undulating w/ eye movements (however, in old RRD the retina may appear smooth and thin)
      • Convex toward front of eye
      • Fixed folds due to proliferative vitreoretinopathy (PVR) almost always indicate a RRD
      • PVR
        • Virtually all RD’s could be repaired were it not for PVR
        • RPE, glial, and other cells grow on both the inner and outer retinal surfaces and on the vitreous face
        • Contraction occurs >fixed folds>equatorial traction>detachment of nonpigmented epithelium of pars plana>generalized retinal shrinkage
        • Causative retinal breaks may reopen, new breaks may occur, or a TRD may develop
        • PVR Classification (1991):
          • Grade A: vitreous haze, vitreous pigment clumps, pigment clusters on inferior retina
          • Grade B: wrinkling of inner retinal surface, retinal stiffness, vessel tortuosity, rolled and irregular edge of retinal break, decreased mobility of vitreous
          • Grade C P 1-12: posterior to equator. Focal, diffuse, or circumferential full-thickness folds*, subretinal strands*,
          • Grade C A 1-12: anterior to equator. Focal, diffuse, or circumferential full-thickness folds*, subretinal strands*, anterior displacement*, condensed vitreous w/ strands
          • * expressed in number of clock hours
    • Tractional Retinal Detachment (TRD)

      • Vitreous membranes caused by penetrating injuries or by proliferative retinopathies (e.g. PDR), can pull the neurosensory retina away from the RPE, causing a TRD
      • Smooth surface, immobile
      • Concave toward front of eye
      • Rarely extends beyond ora serrata
      • May cause tear leading to RRD
    • Exudative Retinal Detachment (ERD)

      • Management usu. NOT surgical
      • Occurs when either retinal blood vessels or RPE is damaged, allowing fluid to pass into the subretinal space
      • Neoplasia and inflammatory dz are leading causes of large ERD
      • Shifting fluid responding to force of gravity
      • Smooth, bullous appearance
      • Etiologies:
        • Idiopathic
          • Coat’s
          • CSCR
          • Uveal Effusion Syndrome
        • Congenital
          • FEVR
          • Optic pit
          • Nanophthalmos
        • Postsurgical
          • PRP
          • RD repair
          • Hemorrhagic choroidal detachment
        • Inflammatory
          • Scleritis
          • Orbital pseudotumor
          • HZO
          • CMV retinitis
          • VKH
          • SO
          • PIC
          • AMPPE
        • Vascular
          • Toxemia of pregnancy
          • AMD
          • Hypertensive retinopathy
          • Diabetic retinopathy
          • Chronic renal failure
          • Cardiac insufficiency
        • Hematologic
          • TTP
          • Leukemia
        • Neoplastic