OcularMD.com -- Disorders of the Retina

Macular Disease

Age-Related Macular Degeneration

Idiopathic Central Serous Chorioretinopathy

Cystoid Macular Edema

Macular Hole
- Full-thickness defect in macula (ILM to PRC outer segs)
- Thought to occur from tangential traction of the cortical vitreous overlying the fovea
- Staging
  1. Foveal detachment -- decreased or absent foveal depression, presence of yellow spot or ring
  2. Early hole formation -- enlarged yellow ring with eccentric or central dehiscence
  3. Fully developed macular hole -- hole with surrounding cuff of subretinal fluid, operculum may be seen in hole
  4. Full-thickness macular hole with posterior vitreous separation
- Special Tests
  - Watzke Slit-Beam Test -- patient notices a break in a thin beam centered over a macular hole
  - FA -- early hyperfluorescence without late leakage
- Disease course
  - Stage 1 holes resolve spontaneously 50% of the time
  - Progress over weeks to years (ave 6 mos)
  - Risk of hole in fellow eye 10-15

Epiretinal Membranes
- Fibrotic membranes which form by cellular proliferation on the inner surface of the retina
- Classified according to severity
  - Cellophane maculopathy -- translucent membrane with minimal distortion
  - Macular pucker -- distinct tissue easily visible on retinal surface with distortion and wrinkling of macular surface
- FA -- vascular tortuosity and straightening; may have leakage if contraction is significant

Pathologic Myopia
- Posterior Staphyloma -- area of ectatic sclera with absent or severely atrophic overlying choroidal or retinal tissue

Angioid Streaks
- Breaks in Bruch's membrane radiating from the optic disc (basophilia, calcification, elastic degeneration)
- 50% associated with systemic disorders (PEPSI)
  - Pseudoxanthoma elasticum -- "plucked-chicken" skin, GI bleed, cardiac disease
  - Ehler-Danlos Syndrome -- hyperextensible skin
  - Paget's Disease -- increased bony mass, high alk phos
  - Sickle Cell and other Hemoglobinopathies (CNVM rare)
  - Idiopathic

Photic Retinopathy
- Solar Retinopathy
- Light toxicity from Ophthalmic Instruments
Drug Toxicity
- Phenothiazines
  - Pigmentary retinopathy (phenothiazines are absorbed by melanin)
  - Thioridazine (Melaril) retinopathy can be seen after >800mg/day for 3-8 weeks
  - Chlorpromazine (Thorazine) retinopathy can be seen after >2400mg/day for 1 year
- Tamoxifen
  - Crystalline retinopathy (may represent products of axonal degeneration)
  - Whorl-like corneal opacities
  - Rarely seen in men undergoing hormonal therapy
  - Other crystalline maculopathies:
    - Canthaxanthine Maculopathy -- skin-tanning agent
    - Oxalosis
    - Bietti's Crystalline Dystrophy -- 3rd decade, autosomal recessive
    - Autosomal Dominant Crystalline Dystrophy -- young female patients
    - Calcified Macular Drusen
    - Talc Retinopathy -- IVDA who inject crushed oral medications containing talc
- Chloroquine and Hydroxychloroquine
  - Chronic use of >250mg/day chloroquine, >6.5mg/day hydroxychloroquine
  - Corneal deposits
  - Bull's-Eye Maculopathy
  - Differential Diagnosis
    - Cone Dystrophy
    - Stargardt's Disease
    - ARMD
    - Benign Concentric Annular Dystrophy
- Methoxyflurane (secondary oxalosis)
- Canthaxanthine

Vascular Disorders

Diabetic Retinopathy

Leading cause of blindness age 20-64
25% of diabetics have diabetic retinopathy
Non-Proliferative Diabetic Retinopathy
- Eye findings
  - Microaneurysms
  - Dilated capillaries
  - Dot-blot nerve-fiber layer hemorrhages
  - Hard exudates
  - Retinal edema
  - Cotton-wool spots
- Special tests
  - IVFA - nonperfusion, edema, small NV, capillary dropout
  - US - tractional retinal detachment
  - Color fundus photos
- Clinically-Significant Macular Edema
  - Defined as:
  - ETDRS study showed benefit of focal or grid laser
- Staging & Follow-Up
  - Mild -- occasional microaneurysms (q12 months)
  - Moderate -- more MAs and scattered hard exudates/cotton-wool spots (q6-12 months)
  - Severe -- 4 quadrants severe retinal hemorrhages OR 2 quadrants of venous beading OR 1 quadrant of severe IRMA (intraretinal microvascular abnormalities) (q3-4 months)
  - Very Severe -- 2 or more quadrants of IRMA (q3-4 months)
Proliferative Diabetic Retinopathy
- Presence of newly formed blood vessels/fibrous tissue arising from the optic disc or retina
- Closure of arterioles -- ischemia -- vasoproliferative factors -- NV of retina, iris, optic nerve
- 26% of pts with a 25-50year history of diabetes have PDR
- Type I DM higher risk than Type II
- Eye findings
  - NVD, NVE
  - Vitreous or preretinal heme
  - Preretinal fibrosis
  - Tractional RD

IVFA -- leakage from NV vessels
Treatment
- May observe closely pts with severe NPDR and low-risk PDR
- Full scatter PRP, 1200-1600 500micron spots 0.1 sec argon in 2 sessions
"High-Risk" PDR

NVD > 1/3 disc area
NVD on or within 1 disc diameter with vitreious or preretinal hemorrhage
NVE at least half of the disc area and vitreous or preretinal hemorrhage

Radiation Retinopathy
Sickle Cell Retinopathy

Types

HgAS most common
HgSS produces the most severe systemic effects
HgSC is least common form, but most common to have retinopathy
HgAC and HbS-Thal are other forms

Eye findings

Salmon patch hemorrhages
Refractile deposits (resorbed hemorrhages)
Black sunbursts (RPE hypertrophy)
Sea-fan neovascularization

Staging

Stage I: Peripheral arterial occlusion
Stage II: Peripheral AV anastomoses
Stage III: Sea-fan neovascularization
Stage IV: Vitreous hemorrhage
Stage V: Tractional retinal detachment

Avoid carbonic anhydrase inhibitors, which can worsen sickling.

Hypertensive Retinopathy

Grading

Grade 1 -- Arterial narrowing
Grade 2 -- Grade 1 plus focal irregularities
Grade 3 -- Grade 2 plus hemorrhage/exudates
Grade 4 -- Grade 3 plus disc swelling

Embolic Diseases

Material	Appearance	Source
Calcium	White	Cardiac Valve
Cholesterol	Yellow	Carotid Disease
Lipid	Yellow	Chest trauma, bone fracture, pancreatitis
Steroid	White	Steroid injection
Fibrin	Grey	Carotid disease
Talc	Refractile	IV injection (IVDA)

Hollenhorst Plaques
Central Retinal Vein Occlusion

Associated with COAG, HTN, DM, Oral contraceptives, and diuretics
Nonischemic

48% resolve completely
30% partially resolve
22% progress to complete occlusion

Ischemic

May have RAPD
90% never improve past 20/400
30% develop NVI by 3 months

Branch Retinal Vein Occlusion

Occlusion of the vein at the site of the AV crossing due to atherosclerotic arteriole compressing adjacent vein confined by a common adventitial sheath.
Associated with HTN
63% of cases involve the superotemporal quadrant
Most spontaneously resolve with vision 20/40 or better
More than 5 disc areas of nonperfusion = increased risk for NV
Focal grid recommended for persistent CME with intact capillary perfusion after 3 months
PRP recommended with retinal or iris neovascularization

Central and Branch Retinal Artery Occlusion

Profound, sudden, severe, painless loss of vision
Macular cherry-red spot
Associated with HTN (67%), Carotid atherosclerosis (50%), DM (25%), Valvular disease (25%)
Associated with GCA in 1-2% of cases
Treatment

Most effective in the first 90 minutes
Reduce IOP by ocular massage or AC tap
Inhalation therapy (95% O2, 5% CO2) for 10 minutes qhour (q4h at night)
Oral acetozolamide, ASA
IV steroids for patients with GCA

Ocular Ischemic Syndrome

Condition attributed to chronic severe carotid artery (90% stenosis) or ophthalmic artery obstruction and subsequent ocular hypoperfusion
Gradual vision loss (weeks to months) with dull, aching pain
Prolonged recovery to bright light
20% bilateral
Follow every 1-2 months to watch for rubeosis & glaucoma

Macroaneurysms

Round or fusiform dilations of the retinal arterioles within the first three orders of bifurcation
Associated with systemic HTN

Perifoveal Telangiectasis

Developmental retinal vascular disorder characterized by ectasia of capillaries (irregular dilatation and incompetance)

Group	Visual Acuity	Demographics	IVFA	Treatment
1A	20/25 to 20/40	Unilateral congenital PFT 40yo men	Temporal half of macula has telangiectatic vessels with macular exudate and edema	Photocoagulation may be helpful; spontaneous resolution possible
1B	20/25 range	Acquired unilateral idiopathic PFT 40yo men	Telangiectatic vessels at one o'clock at the edge of the FAZ with or without exudate	No treatment
2	Better than 20/30	Acquired bilateral PFT 50-60yo men & women Most common type	Temporal foveal vessels, less than 1 DD, with mild dilation and graying of the retina Right angle venules present with some RPE hyperplasia	No treatment
3	Minimal loss to legal blindness	Acquired bilateral PFT with capillary nonperfusion 50-60yo	Telangiectatic vessels with enlarged FAZ with disc pallor; small gold flecks on retinal surface	No treatment

Familial Exudative Vitreoretinopathy

Bilateral autosomal dominant disorder of peripheral vascular development often associated with retinal traction
Genetic defect which induces abnormal development of the hyaloid vascular system

Retinopathy of Prematurity

Risk Factors

Birthweight < 1500g
Gestational Age < 34 weeks
Oxygen therapy
Bronchopulmonary dysplasia
Sepsis
Exchange transfusions
Intraventricular hemorrhage
Necrotizing enterocolitis

Screening

All infants < 1500 g or < 34 weeks GA
Examine at 32 weeks and then every 2 weeks
Disease in Zone 1 or 2 -- examine weekly

Classification

Zone

Centered on disc with diameter of 2x the macula-disk distance
From zone 1 to nasal ora serrate and temporal equator
All other retina outside zone 2

Extent -- number of clock-hours involved
Stage

Demarcation line
Ridge
Ridge with extraretinal fibrovascular proliferation
Subtotal retinal detachment

4A -- Extrafoveal
4B -- Includes fovea

Total Retinal detachment

Treatment (Threshold)

Stage 3 in 5 contiguous OR 8 total clock hours
Stage 3 ROP in Zone 1 or 2
Plus disease

Follow-Up

Higher risk for strabismus, myopia, and astigmatism
Follow for first 5 years of life

Coat's Disease

Telangiectatic and aneurysmal retinal vessels with intraretinal and subretinal exudates
Primary vascular etiology with breakdown of the blood-retinal barrier vs. endocrinologic basis
Juvenile type presents with decreased vision, strabismus, leukocoria
Adult type can be asymptomatic or present with decreased vision
Eye Findings

Localized yellow/green subretinal exudates
Serous RD
Frequently involves macula
Telangiectatic vessels and microaneurysms

Poor prognosis

Von Hippel's Disease

An isolated retinal vascular abnormality characterized by a red/orange intraretinal mass with a dilated feeder artery and draining vein
Autosomal dominant with incomplete penetrance OR sporadic
50% are bilateral
Angiomatous variant is peripheral and without feeder artery/draining vein
Enlarges over time leading to increased exudation, serous detachment, vitreous hemorrhage, or macular pucker
May involute spontaneously
Von Hippel-Lindau Disease

CNS hemangioblastomas
Cysts in kidneys, pancreas, liver, epididymis, ovaries
Renal Cell Carcinoma
Pheochromocytoma

Wyburn-Mason Disease

A rare ocular-cephalic syndrome in which abnormal retinal AV anastomoses are associated with AVMs in the ipsilateral midbrain region
Sporadic
Racemose angioma
Usually no treatment required

Retinal Cavernous Hemangioma

Rare vascular hamartoma composed of clumps of dark intraretinal aneurysms
Eye findings

"Cluster of grapes" -- clumps of intraretinal anuerysms
"Pseudohypopyon" -- layering of RBCs in aneurysms
Fibroglial membrane on surface
Vitreous hemorrhage
Subretinal, intraretinal, preretinal hemorrhages

Anemia
Hyperviscocity

Inflammation

Toxoplasmosis

Toxoplasma gondii

Obliqate intracellular parasite
Spread through cat feces
Tachyzoite invasion leads to retinitis until encysted by host immune response

Demographics

20-70% of persons in US have postitive titers
Only 3% of acquired toxoplasmosis involves the eye
Most cases of retino-choroiditis are congenital

Eye Findings

Fine stellate KP
Mild AC inflammatory reaction
Moderate to severe vitritis -- "Headlight in Fog"
Patches of necrotizing retinitis, often adjacent to pre-existing scar
CME, Optic Neuritis, Vasculitis, scleritis, papillitis
BRVO in areas of retinitis

Special Tests

Toxoplasma IgG and IgM titers
Sabin-Feldman Dye Test -- tests the ability of serum antibody to fix complement and lyse cells
ELISA or indirect fluorescent antibody test
FTA-Abs, PPD, ELISA for Toxocara

Disease Course

Reactivated retinitis resolves over weeks to months
Average number of episodes: 2.7
40% have single episode
Multidrug treatment limits spread

Sulfadiazine
Pyrimethamine
Folinic acid (Leucovorin)
Clindamycin, azithromycin, clarithromycin, spiramycin, minocycline, atovaquone, TMP/SMX are alternatives
Prednisone (20-80mg daily)
Infected Pregnant Women: Sulfadiazine, Clindamycin, or Spiramycin

Follow weekly and observe for medical complications of treatment
CBC bi-weekly while being treated

Sarcoidosis

Multisystem granulomatous disorder of unknown etiology
Increased incidence in African-Americans and Native Scandinavians
90% have intrathoracic involvement
Special Tests

CXR
Biopsy of skin, lymph nodes, lung, liver, or conjunctiva
ACE detects total body granuloma content
Gallium scan of head, neck, mediastinum
Serum lysozyme, serum protein electrophoresis (SPEP), and serum calcium
Kveim Skin Test (No Longer Used) -- nodule induction using a suspension of human sarcoid tissue

Birdshot Retinochoroidopathy

Multiple, bilateral, often symmetric foci of hypopigmentation at the level of the choroid with visual loss secondary to CME and overlying nerve fiber layer atrophy
HLA-A29 association
Blurred vision, floaters, nyctalopia, altered color vision
Females > Males
Eye Findings

Discrete, creamy hypopigmented spots less than 0.5mm in diamter at the level of the choroid that are located predominantly posteriorly
Mild vitreous inflammation
May have attenuation of retinal vasculature with inflammatory sheathing, NFL hemorrhages, subretinal NV, CME, surface wrinkling
Disc edema/atrophy may be present
Minimal anterior segment involvement

May be associated with vitiligo or systemic vasculopathy
Foci of choroidal depigmentation may represent sites of previous accumulation of inflammatory cells below the RPE or focal depigmentation of choroidal melanocytes
Characterized by numerous exacerbations and remissions
20% develop simultaneous, idiopathic glaucoma
Follow every 1-4 weeks during acute phase, 3-6 months during quieter phases

Punctate Inner Choroidopathy

Multifocal choroiditis with small yellow dots at the level of the RPE and inner choroid
Myopic women 16-40 years old
2-6 slightly fuzzy yellow lesions 100-300 microns diameter located at the level of the RPE and inner choroid clustered in the macula and mid-periphery; may have overlying subretinal fluid collections
25% develop choroidal neovascularization
Recurrent symptomatic episodes; no new lesions after 3 months

Acute Posterior Multifocal Placoid Pigment Epitheliopathy

Uncommon illness of young adults
Prodromal flu-like illness followed by the acute onset of multiple bilateral creamy plaques at the level of the RPE and inner choroid
New lesions develop up to 3 weeks after initial onset
Most patients recover good vision over 2-6 weeks
Poorer visual prognosis with foveal involvement (May use short-course steroids, but no proven benefit)

Serpiginous Choroidopathy (Geographic Helicoid Peripapillary Choroidopathy)

Rare, recurrent chorioretinitis affecting 30-60 yo's
Bilateral, fuzzy, pale, yellow subretinal patches extending from the optic nerve with adjacent atrophic scarring
Unknown etiology, possible association with von Willebrand factor
Careful follow-up with Amsler grids to rule out development of choroidal neovascular membranes

Multifocal Choroiditis and Panuveitis

Unilateral disorder of young women
Multiple, recurrent, circular, pale, subretinal inflammatory lesions causing visual loss
Unknown etiology -- thought to be a direct infectious or secondary immune response
Chronic, recurrent disorder lasting months to yeasr with new lesions developing in either eye without regard to location of previous lesions
50% of pts have vision worse than 20/200 in the affected eye
Steroids indicated for patients with CME, vitritis, extensive choroiditis, subretinal neovascularization

Multiple Evanescent White Dot Syndrome

Rare, self-limited disease of acute, unilateral visual loss following viral illness
Young adults, 75% women
Multiple creamy lesions at the level of the RPE
Etiology unknown, may be associated with viral illness precipitating a metobolic disturbance in the RPE-PRC complex
Acuity returns to normal within a few weeks
A chronic, bilateral form with multiple recurrences has been described
Choroidal neovascular membranes are rarely seen

Sympathetic Ophthalmia
Vogt-Koyanagi-Harada Syndrome
Whipple's Disease
Acquired Immunodeficiency Syndrome
Ocular Histoplasmosis
Diffuse Unilateral Subacute Neuroretinopathy
Pneumocystitis
Lyme Disease
Leber's Stellate Neuroretinitis/Cat-Scratch Disease
Cytomegalovirus
Acute Retinal Necrosis Syndrome
Progressive Outer Retinal Necrosis

Parasitic Disorders

Onchocerciasis ("River Blindness")
Toxocara Retinochoroiditis

Hereditary Disorders

Vitelliform Dystrophy (Best's Disease)
Stargardt's Disease/Fundus Flavimaculatus
Leber's Congenital Amaurosis
X-Linked Juvenile Retinoschisis
Retinitis Pigmentosa
Cone Dystrophy
Oguchi's Disease
Congenital Stationary Night Blindness
Fundus Albipunctatus
Choroideremia
Gyrate Atrophy
Central Areolar Choroidal Dystrophy
Pattern Dystrophies of the RPE
Metabolic Diseases
- Cherry-Red Spot
- Mucopolysaccharidosis
- Sphingolipidoses
- Cystinosis

Peripheral Retinal Abnormalities

Posterior Vitreous Detachment
Lattice Degeneration
Cobblestone Degeneration (Pavingstone Degeneration)
Retinal Tears and Holes
Senile Retinoschisis
Retinal Detachment
- Rhegmatogenous
- Tractional
- Exudative
Proliferative Vitreoretinopathy

Vitreous

Developmental Abnormalities
Posterior Vitreous Detachment
Asteroid Hyalosis
Amyloidosis

Posterior Segment Trauma

Commotio Retinae
Traumatic Macular Hole
Retinal Tears and Dialyses
Giant Retinal Tears
Choroidal Effusion
Suprachoroidal Expulsive Hemorrhage
Choroidal Rupture
Choroiretinitis Sclopetaria
Purtscher's Retinopathy
Terson Syndrome
Intraocular Foreign Body
Endophthalmitis
Sympathetic Ophthalmia

Tumors

Malignant Melanoma of the Choroid and Ciliary Body
Choroidal Osteoma
Choroidal Hemangioma
- Retinal Capillary Hemangioma
- Cavernous Hemangioma of the Choroid
Retinal Hamartoma
Intraocular Lymphoma

Major Studies

Diabetic Retinopathy Study
Diabetic Retinopathy Vitrectomy Study
Early Treatment Diabetic Retinopathy Study
Endophthalmitis Vitrectomy Study
Macular Photocoagulation Study
Central Vein Occlusion Study
Branch Vein Occlusion Study