Grand Rounds Terry J. Alexandrou, MD Department of Ophthalmology and Visual Science The University of Chicago 9/7/05

August 9, 2003 HPI: W.A is a 60 y.o A.A. male who presents with a 3 day history of decreased VA and pain in the right eye. Awoke with red, painful right eye. Described decreased VA in right eye as “seeing only black.” C/O bifrontal headache. Denied jaw pain, scalp tenderness, discharge.

HPI: W.A is a 60 y.o A.A. male who presents with a 3 day history of decreased VA and pain in the right eye.

Awoke with red, painful right eye.

Described decreased VA in right eye as “seeing only black.”

C/O bifrontal headache.

Denied jaw pain, scalp tenderness, discharge.

History PMH: None. POH: s/p cataract extraction with PCIOL OU; “few years back” Meds: None All: NKDA FH: N/C SH: Immigrant from Africa, No EtOH, tobacco or IV drug use.

PMH: None.

POH: s/p cataract extraction with PCIOL OU; “few years back”

Meds: None

All: NKDA

FH: N/C

SH: Immigrant from Africa, No EtOH, tobacco or IV drug use.

Exam VA: Without correction: OD- Light perception OS- 20/20 (-2) Pupils: + APD EOM: full Anterior Exam: OD: 3+ injection, severe corneal edema, +NVI, PCIOL OS: mild blepharitis, PCIOL

VA: Without correction: OD- Light perception OS- 20/20 (-2)

Pupils: + APD

EOM: full

Anterior Exam:

OD: 3+ injection, severe corneal edema, +NVI, PCIOL

OS: mild blepharitis, PCIOL

IOP – any guesses? 15 25 46 76

15

25

46

76

76!!!!!!!!!

Differential???

Differential… Diabetic Retinopathy Hypertensive Retinopathy Radiation Retinopathy Ocular Ischemic Syndrome CRVO Hyperviscosity Syndrome

Diabetic Retinopathy

Hypertensive Retinopathy

Radiation Retinopathy

Ocular Ischemic Syndrome

CRVO

Hyperviscosity Syndrome

Next Step… What do you want to do now?

What do you want to do now?

Acute Treatment Alphagan x2 Timolol x2 Diamox x1 Pressure recheck 4 hours later: OD – 45 OS - 17

Alphagan x2

Timolol x2

Diamox x1

Pressure recheck 4 hours later:

OD – 45

OS - 17

Based on the appearance of the fundus photographs, what do you want to check for next?

Based on the appearance of the fundus photographs, what do you want to check for next?

Blood Pressure 202/102 -rechecked several times with manual cuff

202/102

-rechecked several times with

manual cuff

Admitted to Medicine Service Initial B.P in Emergency Department was 206/94 Initially treated with Labetalol 5mg IV pushes Overnight, started on Coreg 6.25 mg bid B.P overnight ranged from 155-162/63-71 Overnight pt. Received timolol x3, alphagan x3, diamox x2 (in addition to initial treatment)

Initial B.P in Emergency Department was 206/94

Initially treated with Labetalol 5mg IV pushes

Overnight, started on Coreg 6.25 mg bid

B.P overnight ranged from 155-162/63-71

Overnight pt. Received timolol x3, alphagan x3, diamox x2 (in addition to initial treatment)

Labs and Tests Chem 10 WNL (glucose of 105) CBC WNL HgBA1C of 6.6 All other labs unremarkable Bilateral Carotid U/S - negative

Chem 10 WNL (glucose of 105)

CBC WNL

HgBA1C of 6.6

All other labs unremarkable

Bilateral Carotid U/S - negative

Day 2 No pain

No pain

Day 2 VA: without correction: OD – LP (but, temporal CF at 2 ft.) OS – 20/20 (-2) IOP: OD – 48 OS – 16 (after total of timolol x4, alphagan x4, diamox x3)

VA: without correction:

OD – LP (but, temporal CF at 2 ft.)

OS – 20/20 (-2)

IOP:

OD – 48

OS – 16

(after total of timolol x4, alphagan x4, diamox x3)

Diagnosis……. Hypertensive retinopathy with ass. CRVO and secondary NVG

Diagnosis…….

Hypertensive retinopathy with ass. CRVO and secondary NVG

Neovascular Glaucoma SYSTEMIC VASCULAR DISEASES *** - Carotid occlusive Disease *** - Carotid artery ligation - Giant cell arteritis - Takayusu disease OCULAR VASCULAR DISEASE *** - Diabetic Retinopathy *** *** - CRVO *** - CRAO - BRVO - Sickle cell retinopathy - Coats Disease - ROP OTHER OCULAR DISEASES - Chronic uveitis - Chronic RD - Endophthalmitis - Retinoschisis INTRAOCULAR TUMORS - Uveal melanoma - Metastatic Carcinoma - Retinoblastoma OCULAR THERAPY - Radiation Therapy TRAUMA

SYSTEMIC VASCULAR DISEASES

*** - Carotid occlusive Disease ***

- Carotid artery ligation

- Giant cell arteritis

- Takayusu disease

OCULAR VASCULAR DISEASE

*** - Diabetic Retinopathy ***

*** - CRVO ***

- CRAO

- BRVO

- Sickle cell retinopathy

- Coats Disease

- ROP

OTHER OCULAR DISEASES

- Chronic uveitis

- Chronic RD

- Endophthalmitis

- Retinoschisis

INTRAOCULAR TUMORS

- Uveal melanoma

- Metastatic Carcinoma

- Retinoblastoma

OCULAR THERAPY

- Radiation Therapy

TRAUMA

Treatment…any thoughts Elevated pressure OD (48) with no view….

Elevated pressure OD (48) with no view….

Cyclocyrotherapy 6 spots of cryo

6 spots of cryo

Retinal Cryotherapy 12 spots of cryo

12 spots of cryo

Day 3 (still an inpatient) POD # 1 s/p retinal and ciliary body cryotherapy for NVG 2/2 CRVO C/O pain in the right eye VA: OD-HM OS: 20/30 IOP: OD-18 OS-12 Anterior Exam: OD - edematous cornea (poor view), with hyphema and fibrinous reaction in the AC; NVI Pt. started on PF q1 hour and atropine bid, along with pressure lowering meds

POD # 1 s/p retinal and ciliary body cryotherapy for NVG 2/2 CRVO

C/O pain in the right eye

VA: OD-HM OS: 20/30

IOP: OD-18 OS-12

Anterior Exam: OD - edematous cornea (poor view), with hyphema and fibrinous reaction in the AC; NVI

Pt. started on PF q1 hour and atropine bid, along with pressure lowering meds

Day 4 (outpatient) POD # 2 s/p retinal and ciliary body cryotherapy for NVG 2/2 CRVO Still with pain in right eye VA: OD-HM OS: 20/30 IOP: OD-21 OS-16 Anterior Exam: OD- edematous cornea, slightly clearer, with 5% suspended hyphema and fibrinous reaction in the AC; PF q2 hours, atropine bid, alphagan, timolol

POD # 2 s/p retinal and ciliary body cryotherapy for NVG 2/2 CRVO

Still with pain in right eye

VA: OD-HM OS: 20/30

IOP: OD-21 OS-16

Anterior Exam: OD- edematous cornea, slightly clearer, with 5% suspended hyphema and fibrinous reaction in the AC;

PF q2 hours, atropine bid, alphagan, timolol

1 Week VA: OD-HM OS- 20/30 IOP: OD-12 OS-13 AC: resolving fibrin

VA:

OD-HM

OS- 20/30

IOP:

OD-12

OS-13

AC: resolving fibrin

2 weeks VA: OD- HM OS – 20/30 AC: No fibrin, D+Q, No NVI; cornea clear………..FINALLY!!! Treatment – PRP right eye F/U Next week

VA:

OD- HM

OS – 20/30

AC: No fibrin, D+Q, No NVI; cornea clear………..FINALLY!!!

Treatment – PRP right eye

F/U Next week

Hypertensive Retinopathy JNC lists retinopathy as 1 of several markers of target-organ damage in hypertension First described by Marcus Gunn Gunn noticed: - arteriolar narrowing - arteriovenous nicking - flame-shaped and blot-shaped retinal hemorrages - cotton-wool spots - swelling of the optic disc

JNC lists retinopathy as 1 of several markers of target-organ damage in hypertension

First described by Marcus Gunn

Gunn noticed:

- arteriolar narrowing

- arteriovenous nicking

- flame-shaped and blot-shaped retinal hemorrages

- cotton-wool spots

- swelling of the optic disc

Pathophysiology 1) Vasoconstrictive Stage – initially, seen as generalized narrowing of retinal arterioles 2) Persistently Elevated BP – more severe generalized and focal areas of arteriolar narrowing; AV nicking, and alterations in arteriolar light reflex (copper wiring) 3) Exudative Stage – microaneurysms, hemorrhages, hard exudates, cotton-wool spots, swelling of the optic disc (if severely elevated blood pressure)

1) Vasoconstrictive Stage – initially, seen as generalized narrowing of retinal arterioles

2) Persistently Elevated BP – more severe generalized and focal areas of arteriolar narrowing; AV nicking, and alterations in arteriolar light reflex (copper wiring)

3) Exudative Stage – microaneurysms, hemorrhages, hard exudates, cotton-wool spots, swelling of the optic disc (if severely elevated blood pressure)

Epidemiology > 50 million people in the US affected by hypertension Prevalence of 2-15 % for various signs of retinopathy

> 50 million people in the US affected by hypertension

Prevalence of 2-15 % for various signs of retinopathy

Classification of Hypertensive Retinopathy Grade 0 No changes Grade 1 Barely detectable arterial narrowing Grade 2 Obvious arterial narrowing with focal irregularities Grade 3 Grade 2 plus retinal hemorrhages and/or exudate Grade 4 Grade 3 plus disc swelling

Grade 0 No changes

Grade 1 Barely detectable arterial narrowing

Grade 2 Obvious arterial narrowing with focal irregularities

Grade 3 Grade 2 plus retinal hemorrhages and/or exudate

Grade 4 Grade 3 plus disc swelling

Treatment Blood pressure Control Chronic hypertensive retinopathy alone rarely, if ever, results in significant vision loss.

Blood pressure Control

Chronic hypertensive retinopathy alone rarely, if ever, results in significant vision loss.

Evidence of hypertensive retinopathy can be used for risk stratification of other systemic diseases associated with hypertension

Evidence of hypertensive retinopathy can be used for risk stratification of other systemic diseases associated with hypertension

Atherosclerosis Risk in Communities Study Multisite cohort study 5 year risk of stroke of participants with both hypertensive retinopathy and cerebral lesions on MRI (compared to those with neither of these 2 findings) was 18.1. - Among participants with only cerebral lesions on MRI only, the RR of stroke was 3.4.

Multisite cohort study

5 year risk of stroke of participants with both hypertensive retinopathy and cerebral lesions on MRI (compared to those with neither of these 2 findings) was 18.1.

- Among participants with only cerebral lesions on MRI only, the RR of stroke was 3.4.

CRVO

CRVO

Pathogenesis Thrombus in the central retinal vein at the level of the lamina cribosa, often secondary to atherosclerosis of the neighboring central retinal artery.

Thrombus in the central retinal vein at the level of the lamina cribosa, often secondary to atherosclerosis of the neighboring central retinal artery.

Risk Factors Age > 50 DM Htn Hyperviscosity syndromes Glaucoma

Age > 50

DM

Htn

Hyperviscosity syndromes

Glaucoma

Classification of CRVO 1) Non-ischemic – ~75-80% have this milder form 2) Ischemic - ~20-25% have this severe form

1) Non-ischemic – ~75-80% have this milder form

2) Ischemic - ~20-25% have this severe form

Non-Ischemic CRVO Symptoms – 1) mild to moderate decrease in VA (can range from normal to CF however); 2) intermittent blurring; 2 pain is rare Signs – 1) APD is rare; 2) dot and flame hemorrhages in all 4 quadrants; 3) optic nerve head swelling; 4) engorgement and tortuosity of retinal veins; 5) macular hemorrhage or edema; 6) rarely is there neovascularization of either the anterior or posterior segment (<2%)

Symptoms – 1) mild to moderate decrease in VA (can range from normal to CF however); 2) intermittent blurring; 2 pain is rare

Signs – 1) APD is rare; 2) dot and flame hemorrhages in all 4 quadrants; 3) optic nerve head swelling; 4) engorgement and tortuosity of retinal veins; 5) macular hemorrhage or edema; 6) rarely is there neovascularization of either the anterior or posterior segment (<2%)

Progression of Non-Ischemic to Ischemic CRVO Central Vein Occlusion Study - 34 % of eyes initially diagnosed with non-ishemic CRVO progressed to ischemic variant within 3 years; (15% converted within first 4 months)

Central Vein Occlusion Study

- 34 % of eyes initially diagnosed with non-ishemic CRVO progressed to ischemic variant within 3 years; (15% converted within first 4 months)

Ischemic CRVO 1) Symptoms – 1) Acute, markedly decreased visual acuity (usual presenting complaint, VA ranges from 20/200 to LP) ; 2) Pain (if neovascular glaucoma has already developed) 2) Signs – 1) APD is common; 2) Extensive 4 – quadrant retinal hemorrhages and edema; 3) Marked venous Dilation; 4) Anterior Segment Neovascularization (60 % or higher) 5) Neovascular glaucoma – can occur within 3 months of disease onset (90 day glaucoma), often resulting in intractably elevated IOP’s; 6) Neovascularization of optic disc and retina may be seen, but not as common;

1) Symptoms – 1) Acute, markedly decreased visual acuity (usual presenting complaint, VA ranges from 20/200 to LP) ; 2) Pain (if neovascular glaucoma has already developed)

2) Signs – 1) APD is common; 2) Extensive 4 – quadrant retinal hemorrhages and edema; 3) Marked venous Dilation; 4) Anterior Segment Neovascularization (60 % or higher) 5) Neovascular glaucoma – can occur within 3 months of disease onset (90 day glaucoma), often resulting in intractably elevated IOP’s; 6) Neovascularization of optic disc and retina may be seen, but not as common;

Diagnosis 1) Characteristic fundus photos – 2) FANG in ischemic CRVO– most useful ancillary test; Eyes with 10 disc areas or greater of non-perfusion are classified as ischemic - demonstrates marked hypofluorescence – secondary to blockage from extensive retinal hemorrhages or to capillary non-perfusion - optic nerve head leakage - macular edema 2) FANG in non-ischemic CRVO – - staining along retinal veins - microaneurysms - dilated optic nerve head capillaries - minimal or absent retinal capillary non-perfusion

1) Characteristic fundus photos –

2) FANG in ischemic CRVO– most useful ancillary test; Eyes with 10 disc areas or greater of non-perfusion are classified as ischemic

- demonstrates marked hypofluorescence – secondary to blockage from extensive retinal hemorrhages or to capillary non-perfusion

- optic nerve head leakage

- macular edema

2) FANG in non-ischemic CRVO –

- staining along retinal veins

- microaneurysms

- dilated optic nerve head capillaries

- minimal or absent retinal capillary non-perfusion

Treatment If Neovascular Glaucoma – CVOS demonstrated PRP was recommended in eyes where iris neovascularization was present, however prophylactic PRP did not show statistical significance in prevent neovascularization. If Macular Edema – CVOS showed that macular grid laser reduced angiographic evidence of macular edema, however there was no difference in VA of treated vs. untreated eyes; Recent study demonstrated intravitreal kenalog effective in reversing CME and improving VA in recent-onset non-ischemic CRVO at 6 months, but results not maintained at 1 year Laser – induce Chorioretinal Venous Anastomosis Radial neurotomy

If Neovascular Glaucoma – CVOS demonstrated PRP was recommended in eyes where iris neovascularization was present, however prophylactic PRP did not show statistical significance in prevent neovascularization.

If Macular Edema – CVOS showed that macular grid laser reduced angiographic evidence of macular edema, however there was no difference in VA of treated vs. untreated eyes; Recent study demonstrated intravitreal kenalog effective in reversing CME and improving VA in recent-onset non-ischemic CRVO at 6 months, but results not maintained at 1 year

Laser – induce Chorioretinal Venous Anastomosis

Radial neurotomy

Typical Course of CRVO 50 % of non-ischemic CRVO patients deteriorate to 20/200 or worse 90 % of ischemic CRVO patients have VA of 20/200 or worse 7% of CRVO patients develop a venous occulsion in the fellow eye within 2 years (risk ~ .9 % per year)

50 % of non-ischemic CRVO patients deteriorate to 20/200 or worse

90 % of ischemic CRVO patients have VA of 20/200 or worse

7% of CRVO patients develop a venous occulsion in the fellow eye within 2 years (risk ~ .9 % per year)