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LARGEST STUDY ON CHINESE AMERICANS PUBLISHED

LARGEST STUDY ON CHINESE
AMERICANS PUBLISHED

USC Ophthalmology Researchers Find More
Effective Treatments For Blinding Eye Diseases

EDUCATION

Case Study: A Stormy Night

Greer Ameri
Presenter: Christine Greer, MD Discussant: Hossein Ameri, MD, PhD
 

History

  • 47-year-old Hispanic male with hyperlipidemia and hypertension and history of severe non-proliferative diabetic retinopathy
  • Presents complaining of worsening vision in right eye
  • Previously 20/40 OU
  • Status post pan-retinal photocoagulation (PRP) OU in April 2016

Exam Findings

  • VA: 20/200 || 20/40
  • Pupils: Round and Reactive OD and OS, 3+ RAPD OD
  • IOP: 15, 17
  • Extraocular movements intact
  • Slit lamp exam: normal, aside from trace cataract OU
Figure 1
Figure 1: Optos photo of right eye. Media clear, note blurring of superior margin of disc without obscuration of the small or large disc vessels. Mild-moderate venous tortuosity, loss of foveal reflex, dot blot hemorrhages, flame hemorrhages in four quadrants. Scattered cotton wool spots. Panretinal photocoagulation (PRP) in the periphery.
Figure 2
Figure 2: Optos photo of left eye. Media clear, disc with sharp margins, diffuse cotton wool spots along the arcades. Macula flat.
Figure 3
Figure 3: Laminar phase fluorescein angiogram of right eye. Note venous tortuosity, widespread patches of capillary drop out, microaneurysms in four quadrants, window defects in the location of PRP scars.
Figure 4
Figure 4: Late venous phase fluorescein angiogram of right eye. Again, there is venous tortuosity, extensive capillary drop out with minimal macular leakage, microaneurysms in four quadrants and window defects in the location of PRP scars.
Figure 5
Figure 5: Late venous phase fluorescein angiogram of left eye, notable for microaneurysms, capillary drop out, diffuse late leakage with minimal macular leakage, window defects in the location of PRP scars.
Figure 6
Figure 6: OCT macula of right eye. Poor study (3/10 signal strength) demonstrating marked intraretinal fluid.

 

Differential Diagnosis

  • Worsening diabetic retinopathy with macular edema
  • Central Retinal Vein Occlusion (CRVO)/ Branch Retinal Vein Occlusion (BRVO)
  • Hyperviscosity retinopathy
  • Waldenstrom macroglobulinemia
  • Multiple myeloma
  • Blood dyscrasias
  • Ocular Ischemic Syndrome

Diagnosis

  • Central Retinal Vein Occlusion (CRVO)
    • Clinical features of CRVO
      • Ischemic versus non-ischemic
      • Intermediate or indeterminate when they are neither clearly ischemic or non-ischemic
    • Non-ischemic, mild or venous stasis retinopathy
      • Good VA, no RAPD, mild visual field changes
      • Mild dilation and tortuosity of all branches of the central retinal vein as well as dot- and flame-shaped hemorrhages in all quads of the retina
      • Macular edema
      • Fluorescein angiography: prolonged circulation time, breakdown of capillary permeability, minimal nonperfusion areas
      • Anterior segment Neovascularization is uncommon
    • Ischemic, complete, non-perfused or hemorrhagic retinopathy
      • Poor vision
      • RAPD
      • Dense central scotoma
      • Marked dilation and tortuosity of all branches of the central retinal vein as well as more extensive dot- and flame-shaped hemorrhages in all quads of the retina
      • Fluorescein Angiography: prolonged circulation time, breakdown of capillary permeability, widespread capillary nonperfusion
      • IRIS NEOVASCULARIZATION IN ischemic CRVO
        • Up to 60 percent
        • Three to five months after the onset of symptoms
        • Highest predictor is poor presenting visual acuity (CVOS: Central Vein Occlusion Study)
    • CRVO: Risk Factors
      • Age: 90 percent are over age 50
      • Hypertension
      • Diabetes mellitus
      • Hyperlipidemia
      • Elevated IOP or POAG
    • Retinal Vein Occlusion: Proposed elements of pathophysiology
      • Retina drained by occluded vessels becomes ischemic and produces hypoxia-related gene products, including VEGF
      • Macular edema after CRVO is typically due to diffuse capillary leakage and not due to focal microaneurysmal dilatation similar to that seen in early diabetic retinopathy
      • Retinal nonperfusion (RNP) has been demonstrated to progress over time
      • It is presumed that high levels of VEGF contribute to progressive RNP
    • Contributions of USC Roski Eye Institute ophthalmologist Ronald L. Green, MD: histopathologic study of 29 eyes with CRVO:
Figure 7
Figure 7: From Ronald L. Green, MD, histopathology. Section through optic nerve with patent central retinal artery (asterisk), to the right thrombus in the central retinal vein.
Figure 8
Figure 8: From Ronald L. Green, MD, histopathology. Section through optic nerve at the optic nerve head. Again, patent central retinal artery (asterisk), posteriorly, at the level of the lamina cribrosa, thrombus in the central retinal vein (arrow head), diffuse hemorrhage in the retrolaminar portion of the optic nerve nasally (arrows).
Figure 9
Figure 9: From Ronald L. Green, MD, histopathology. Higher power of thrombus showing entrapped pockets of erythrocytes proximally (asterisks), aggregation of platelets (circle), fibrin (arrowhead) and adherence to wall of vein where endothelium is absent (arrows).

 

  • Average age: 62.9 years
  • Men: 61 percent
  • In 24 eyes, the thrombosed area at the level of and posterior to the lamina cribrosa
  • In five eyes, anterior to the lamina cribrosa
  • Fresh thrombus observed in three, recanalized in 26, endothelial cell proliferation in 14, chronic inflammation in 14, arterial occlusive disease in 7, Cystoid Macular Edema in 26
  • The Central Retinal Vein narrows as it traverses the lamina cribrosa in the normal eye
  • Further narrowing or increased turbulence of flow through a partial barrier may predispose to CRVO
  • In systemic hypertension, there is a thickening of the wall of the artery, which may impinge on the vein (their juxtaposition)
  • Flow through this portion of the vein can become turbulent and damage the endothelium

Treatment of CRVO

  • CVOS: GRID
    • Eyes with VA 20/50 to 20/200 with angiographic Macular Edema due to CRVO
    • Randomly assigned to grid photocoagulation (n=77) v no treatment (n=78)
    • Significantly reduced the amount of macular edema by FA
    • At 12 months annual visit, no measurable macular edema was present in 21 (31 percent) of treated eyes
    • But no differences between groups in visual acuity
    • Conclusion: Grid macular laser does not improve vision in macular edema secondary to CRVO
  • CVOS: Panretinal Photocoagulation (PRP)
    • Question: can PRP prevent anterior segment neovascularization in ischemic CRVO, or is it more appropriate to treat once neovascularization occurs?
    • Methods: 181 eyes randomly assigned to treatment with PRP versus close observation
    • Results: The development of neovascularization was not statistically significant different between groups
    • Degree of neovascularization correlated with amount of non-perfused retina (P=0.0001) and extent of retinal hemorrhage (P=0.03)
    • Conclusion: prophylactic PRP does not prevent anterior segment neovascularization in ischemic CRVO
  • Treatment for macular edema in CRVO
Figure 3

 

  • The Relate Trial
  • Double-masked randomized controlled trial
    • Comparing 0.5mg and 2mg ranibizumab monthly injections for six months in patients with macular edema from retinal vein occlusion (RVO)
  • To determine if scatter-grid reduces the need for injections and improves long-term outcomes in patients with RVO
    • 81 patients with RVO: 39 with CRVO and 42 with BRVO
    • 77 made it to six months
    • 77 re-randomized to PRN (as needed) arms: Ranibizumab + laser or Ranibizumab only for recurrent macular edema
    • Comparison of visual outcomes in patients treated with 0.5 v 2.0mg Ranibizumab
      • No differences across groups

    Figure 3
     

    • Central subfield thickness (CST) in patients treated with 0.5 v 2.0 mg Ranibizumab
      • BRVO: No statistically significant difference between groups
      • CRVO: Significantly decreased CST in 2.0mg group at 24 weeks compared to 0.5mg
Figure 3

 

  • Scatter + Grid laser on visual outcomes:
    • Overall, no significant differences in BCVA or CST between injections or injections + laser groups from week 24 to 144
  • In addition, mean number of injections greater for CRVO patients in the laser + injections group (p=0.5)

Summary and Future Directions

  • No role for laser for treatment of CME or for prevention of neovascularization
  • Anti-VEGF mainstay of treatment
  • No difference in 0.5 v 2.0 mg Ranibizumab per Relate Trial
  • Identifying known risk factors and who warrants work up
    • <50
    • No known hypertensive disease
  • Understanding mechanism of ischemia in CRVO may lead to alternative treatments and drug development

References

  • A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995 Oct;102(10):1434-44.
  • McCannel CA, Atebara NH, Kim SJ, Leonard BC, Rosen RB, Sarraf D, et al. Retina and Vitreous. In: Louis B Cantor, Christopher J Rapuano, George A Cioffi, editors. Basic and Clinical Science course. San Francisco: American Academy of Ophthalmology; 2017.
  • Tan MH, McAllister IL, Gillies ME, Verma N, Banerjee G, Smithies LA, et al. Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion. Am J Ophthalmology. 2014 Jan;157(1):237-247.
  • Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014 Sep;121(9):1783-9.
  • Campochiaro PA, Hafiz G, Mir TA, Scott AW, Solomon S, Zimmer-Galler I, et al. Scatter Photocoagulation Does Not Reduce Macular Edema or Treatment Burden in Patients with Retinal Vein Occlusion: The RELATE Trial. Ophthalmology. 2015 Jul;122(7):1426-37.
  • Mir TA, Kherani S, Hafiz G, Scott AW, Zimmer-Galler I, Wenick AS, et al. Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion. Ophthalmology. 2016 Mar;123(3):625-34.
  • Green WR, Chan CC, Hutchins GM, Terry JM. Central Retinal Vein Occlusion. Retina. 2005 Jul;25(SUPPLEMENT):27-55.
  • Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report Ophthalmology. 1995 Oct;102(10):1425-33.

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Produced by: Monica Chavez, John Daniel, Joseph Yim and Dr. Vivek Patel
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