Retinal vascular disease: Diabetic Retinopathy, Branch Retinal Artery Occlusion, Central Retinal Artery Occlusion, Branch Retinal Vein Occlusion, Central Retinal Vein Occlusion, Hypertensive Retinopathy, Eale's Disease

1. Retinal Vascular Diseases:
Diabetic Retinopathy
Artery and Vein Occlusion
Hypertensive Retinopathy
Eale’s Disease
Rabindra Adhikary
M.Optom 1st Batch
30th July 2019, Tuesday
Facilitator
Dr. Sanjita/Dr. Sushma

2. WELCOME

3. Retinal Circulation
• Arterial System:
– Central Retinal Artery
• Enters the globe approx 1cm behind the globe
– Intima – single layer of endothelium
– Media – smooth muscle
– Adventitia – loose connective tissue
– Arterioles
• Arise from CRA
• Walls contain smooth muscle

4. Arterial System contd.
• Capillaries
– Retinal capillaries (RC) supply inner 2/3rd of retina
– Choriocapillaries  outer third
– Inner Plexus (capillary network)Ganglion cell
layer
– Outer Plexus Inner Nuclear layer
– RC lack smooth muscle and elastic tissue

5. Retinal Capillaries
• Wall consists of
– Endothelial cells: Inner Blood-Retinal Barrier
– The basement membrane
– Pericytes
• Its pseudopodial processes envelop the arteries
• Have contractile properties
• Thought to participate in autoregulation of
microvascular circulation

6. Venous system
• Small venules
– larger than capillaries
– Similar structure
• Large venules
– Contain smooth muscle
– Merge to form veins
• Veins
– Smooth muscle + elastic tissue
– distensible

7. Diabetic retinopathy
• Progressive changes in the retinal
microvasculature in pt with DM
Epidemiological facts**
• Type I DM
– First 5 years  low risk of DR
– 5-10 years  27% develop DR
– >10 years  71-90% develop DR
• Type II
– 10 years of Diagnosing DM
• 67% of people develop DR
• 10% develop PDR
**Klein et al: https://www.sciencedirect.com/science/article/pii/S0161642095310524

8. • Many pt who have DM are unaware of their
retinopathy
– A study on Joslin center on self-awareness of DR
demonstrated 83% of pt with DR @ their first visit
were unaware**
patient Education is a must!
**Joslin's Diabetes Mellitus: Edited by C. Ronald Kahn

9. Pathogenesis of DR
• Vasoproliferative Factors
– Retina and RPE release VF like VEGF
– VEGF neovascularization
– VEGF direct role in proliferative retinal vascular
abnormalities in DM
– Is also responsible for DME
• Platelets and blood viscosity
– Due to platelets abnormalities and ↑ed blood viscosity
• plasma perfusion out of vessels
• capillary occlusion
• Focal areas of ischemia

10. • Aldose Reductase
– Converts glucose sorbitol
– Galactose  galactitol
– These alcohol can’t escape easily out of cells
• ↑ed intracellular concn
• Water enters by osmosis
• This AR abundant in lenticular cells are responsible for
cataract
– Same mechanism is believed to occur in DR and DN
because
• AR are also present in retinal pericytes and schwann cells

11. Diagnostic tests
• Ophthalmoscopy or fundus biomicroscope
– Microaneurysms are the hallmark sign
• Blood Inv:
– FBS
– Glucose tolerance test
– HbA1C
• FFA
– Severity of DR, extent of leakage, macular edema
– Capillary nonperfusion
– Confirm neovascularization

12. • OCT
– Retinal thickness, macular edema
– Valuable for future monitoring
• Color vision
– Earlier blue-yellow discrimination loss
– Later red-green affected
• Dark adaptation
– Delayed
• poor recovery in the photo-stress test

13. Important features of DR
• Microaneurysm
– Hyperglycemia weakens the capillaries walls
– Small outpouchings of vessel lumen
– Sometimes ruptures deep into internal limiting
membrane
• Dot & blot hemorrhage

14. Micro-aneurysm vs dot hemorrhage
• FFA
– Hyperfluorescene in contrast to hemorrhage

15. Exudates
• Soft exudates are caused by chronic localized
retinal edema
– At the junction of normal and edematous retina
• Compositions:
– Lipoprotein
– Lipid filled macrophages
– (hyperlipidemia ↑es the likelihood)
• Located mainly in outer plexiform layer

16. Hard Exudates
• Waxy yellow lesions
• Distinct margin
• Arranged in clumps
• When leakage ceases
– Disappear by the time

17. Cotton wool spots
• Accumulation of neuronal debris within the
NFL
• Results from:
– Ischemic disruptions of nerve axons
• Fluffy whitish superficial lesion obscures blood
vessels

19. IRMA
• Intra-retinal microvascular abnormalities are
arterio-venular shunts running from retinal
arterioles to venules
– Bypasses the capillary bed
– In areas of capillary hypoperfusion

21. ETDRS classification

23. High Risk Characteristics (HRC) of PDR
• Diabetic Retinopathy study (DRS)
– NVD ¼ - 1/3rd of disc area
– Any NVD with Vitreous Hemorrhage
– NVE > ½ of disc area + vitreous or pre-retinal
Hemorrhage
NVD = neovascularization @ Disc
NVE = Neovascularization Elsewhere

24. Clinically Significant Macular Edema
• CSME is detected on clinical examination:
– Retinal thickening within 500 μm of the center of
the macula
– Exudates within 500 μm of the center of the
macula, if associated with retinal thickening; the
thickening itself maybe outside the 500 μm
– Retinal thickening one disc area (1500 μm) or
larger, any part of which is within one disc
diameter of the centre of the macula

26. Stages of DR

27. Laser Therapy
• PRP
– ETDRS has said PRP significantly retards the
development of HRC in eyes with severe NPDR
and DME
• Focal Laser
– Photocoagulate all leaking micro-aneurysms
further than 500micrometer from fovea
– Place a grid of 100-200 micrometer burns in areas
of diffuse capillary nonperfusion

28. Medical Therapy
• Corticosteroid Therapy
– Monotherapy of intravitreal triamcinolone acetonide
over 2 years of Tx
• Not superior than laser photocoagulation alone in DME**
– So, most preferably used in conjunction with laser
therapy.
– Intravitreal dexamethasone implant (Ozurdex)
containing 700 mcg dexamethasone is also popular
after it was approved by FDA.
– However, not a Tx of choice when anti-VEGF are
available
**https://jamanetwork.com/journals/jamaophthalmology/article-abstract/1149508

29. Medical Therapy
• Anti-angiogenesis agent
– Superior effect to laser and corticosteroid with relatively
good safety profile
– Primary Tx choice for fovea involving DME
– Common Anti-VEGF
• Ranibizumab (Lucentis)
• Pegaptanib sodium (macugen)
• Bevacizumab (Avastin)
• Aflibercept (Eylea)
– 1st FDA approved anti-VEGF for DME
• Ranibizumab (0.3mg)  prohibitive cost
• So drug of choice worldwide  Bevacizumab

30. • Drawbacks of anti-VEGF
– Cost
– Needs repeated administration of injection
– Risk of endophthalmitis

31. Medical Therapy
• Antihypertensives
– United Kingdom Prospective Diabetes Study (UKDPS)**
• Compared between 2 groups
• Diabetic with tight control of BP (<150/85): Group I
• Diabetic with less tight control of BP (<180/105): Group II
• Group I showed 37% reduction of risk in developing retinal
microvascular changes
– So, angiotensin-Converting enzyme inhibitor (ACEIs) or
beta-blockers are beneficial to stop the progression of
DR
**https://www.bmj.com/content/317/7160/703

32. Retinal Artery Occlusion
• Major cause
– Atherosclerosis related embolism & thrombosis
• Minor cause
– Inflammation in and around the vessels
• Giant Cell Arteritis (GCA)
• Systemic Lupus (SLE)
• Polyarteritis nodosa
• Vasospasm (migraine), etc.

33. Assessment
• Pulse
• BP
• Cardiac auscultation
• ECG
• ESR / Plasma Viscosity / C-reactive Protein to identify
GCA
• CBC, glucose, lipid, urea and electrolytes
• Selected case: carotid imaging, Cranial MRI or CT scan,
Echocardiography, chest x-ray, additional blood tests
like TFT, autoantibodies, Rhematoid Factor

34. BRAO
• Symptoms: sudden & profound sectoral loss of
vision
• go unnoticed, particularly if central vision is
spared.
• VA is variable. In patients where central vision
is severely compromised, the prognosis is
commonly poor unless the
– obstruction is relieved within a few hours
• RAPD : +mild to moderate

35. Clinical picture of Fundus
• Cattle trucking / boxcarring
– Segmentation of blood column in artery/vein
• Cloudy white edematous (ground glass) retina
corresponding to the area of ischemia.
• One or more occluding emboli
– especially at bifurcation points.
• The affected artery is likely to remain attenuated.
– Occasionally, recanalization makes –ve
ophthalmoscopic signs
• VF confirms the defect  rarely recovers

37. • FA shows delay in arterial filling and
hypofluorescence involved segment
– blockage of background fluorescence by retinal
swelling

38. • Patient education
• Confirm all the systemic management has
been initiated
• Review in 3 months

39. CRAO
• Sudden and profound visual loss
– Painful only in case of GCA
• VA severely affected
– unless cilioretinal artery (15-50% eyes do have
back-up arterial supply from posterior ciliary
circulation
• RAPD + Marked

40. Fundus Features of CRAO
• ‘cherry-red spot’ appearance
– orange reflex from the intact choroid stands out at
the thin foveola, in contrast to the surrounding
pale retina
• occasional small hemorrhage
• Emboli are visible in 20%, when Nd : YAG
embolysis may be considered
• Retinal signs can sometimes be subtle; retinal
edema may take several hours to develop

42. • Around 2% of eyes with CRAO develops retinal
or disc neovascularization
• Rubeosis iridis upt 20% of affected eyes
• OCT may show a highly reflective embolic
plaque within the superficial optic nerve head.
• FA shows a variable delay in arterial filling and
masking of background choroidal fluorescence
by retinal edema.

44. • Electroretinography may be helpful to
– distinguish from optic nerve disease,
– a diminished b-wave is present

45. reviews
• 3-4 weeks by ophthalmologist
• Appropriate systemic management

46. Acute Retinal Artery Occlusion
• Emergency management
– Irreversible visual loss unless the retinal circulation is
re-established before developing retinal infarction
– So following measures can be adopted if presentation
is within 24-48 hours
• Posture-supine position
• Ocular massage (10-15 sec & release for 3-5 min.)
• Anterior Chamber paracentesis : 0.1-0.2ml (??)
• Topical apraclonidine 1%, timilolol 0.5%, and IV acetazolamide
500mg
• Rebreathing into the paper bag (↑blood CO2 & respiratory
acidosis)

47. Retinal Vein Occlusion
• Assessment
– BP
– ESR/PV
– CBC
– RBS
– HDL
– Urea/electrolytes/creatinine
– TFT
– ECG

48. BRVO
• VA reduced if central region involved
– Metamorphopisa
– Perioheral occlusion maybe asymtomatic
• 50% of untreated eyes retain VA >6/12
• About a quarter achieve <6/60
• NVI and NVG much less common than CRVO

49. Fundus Features BRVO
• Dilatation and tortuosity of the affected
venous segment, with flame-shaped and
dot/blot hemorrhages
• Most affected quadrant – superotemporal
• acute features usually resolve within 6–12
months leaving venous sheathing and
sclerosis, and variable persistent/recurrent
hemorrhage

51. • most common cause of persistent poor vision
– Chronic macular edema
• FA demonstrates peripheral and macular
ischemia (capillary non-perfusion, staining of
vessel walls)
• OCT allows
Quantification
of edema

52. Treatment/Management
• If VA is 6/9 or better  wait and watch
• If VA <6/12 , FFA in 3 months
• NVE or NVD  sectoral photocoagulation
• NVI urgent sectoral PRP

53. Tx: sectoral laser

54. Tx: Intravitreal Anti-VEGF Inj
CME treated with intravitreal bivacizumab after 4
weeks

55. CRVO
• Occlusion at or posterior to lamina cribrosa

56. Pathogenesis
Loss of vessel wall
integrity
Altered Blood
Flow
Hypercoaguable
state of blood
This disturbance leads to thrombus formation and vein occlusion

57. Fundus Finding
• Extensive hemorrhage in the posterior pole
Blood and thunder appearance

58. FFA Finding
• Delayed arterio-venous transit
• Macular edema
• Staining along the retinal veins
• NVD, NVE

60. Management of CRVO
• For macular edema
– Tx only when VA is <6/9 and macular thickening is
>250 micro meter
– Unlikely to be benefit if VA< 6/120
– Current standard of are
• Intra-vitreal anti-VEGF or
• Dexamethasone implant

61. Management of CRVO
• PRP for NVI/angle
– With adjunctive therapy of anti-VEGF
• Vitrecctomy or endolaser for Vitreous Hge

62. Hypertensive Retinopathy
• The changes in the retina that we can see
from funduscopy, which is associated directly
to the sustained systemic hypertension
– Vasoconstriction
– Arterioslcerosis leading to AV-nipping
– Disruption of tight junction of inner retinal blood
barrier  permeability, leakage and hemorrhage
– All these features among others represent the
retinopathy

63. Grade I
• Mild generalized retinal arteriolar narrowing

64. Grade II
• Focal arteriolar narrowing and arteriovenous
nipping
• A ‘copper wiring’ opacified appearance of
arteriolar walls

65. Grade III
• Grade 2 +
• retinal hemorrhages (dot, blot, flame)
• Exudates
(chronic retinal edema may result in the
deposition of hard exudates around
the fovea as a ‘macular star’ )
• cotton wool spots.

66. Grade IV
• Grade 3+ optic disc swelling
• this is a marker of malignant hypertension

67. AV Crossing Changes
• Salus’s sign:
– Deflection of retinal vein as it crosses the
arteriole.
• Gunn’s sign:
– Tapering of the retinal vein on either side of the
AV crossing.
• Bonnet’s sign:
– Banking of the retinal vein distal to the AV
crossing.

68. • Elsching spot: hypertensive choroidopathy
with focal choroidal infarcts seen as black
spots surrounded by yellow haloes

69. Management

70. Eales Disease
• Idiopathic occlusive peripheral periphlebitis
• Important cause of visual morbidity in young
males of Indian subcontinent
• Symptoms:
– Floaters and sudden blurring of vision due to VH
• Signs:
– MILD anterior uveitis
– Fundus sign typically bilateral but asymmetrical

71. • Peripheral periphlebitis, sheathing, superficial
retinal hemorrhages and sometimes cotton
wool spots. Pigmented chorioretinal scars may
be seen

72. • Peripheral capillary nonperfusion
• BRVO
• Microaneurysm
• Vascular shunts
• Neovascularization
• Recurrent VH

73. • complications
– Tractional RD
– Macular epiretinal membrane
– Neovascular glaucoma
• Investigations
– To R/O other causes of vasculitis (sarcoidosis,
tuberculosis) and peripheral retinal
neovascularization (eg. Hemoglobinopathies)

74. Tx of Eale’s
• Steroid
– Periocular, systemic, topical, and intravitreal steroids 
helpful in the inflammatory stage.
• Antitubercular Tx
– Selected pt in combination with steroid
– Not widely agreed upon
• Scatter photocoagulation or cryotherapy
– Of nonperfused retina to stop neovascularization
• Intra-vitreal VEGF inhibitors- researrch ongoing
• Vitrectomy for persistent VH, tractional RD and
macular epiretinal membrane

75. References