Central Retinal Vein Occlusion

Management of CRVO(continued)

B. SURGICAL OR INVASIVE TREATMENTS

• Fibrinolytic or thrombolytic agents: The theoretical objective of this therapy is to dissolve the preformed thrombus in the central retinal vein. From the studies reported in the literature there is little evidence that these have any beneficial effects.⁶ Moreover, administration of these drugs can cause a significant hazard of bleeding, e.g., vitreous and cerebral hemorrhage and other systemic complications.
  
  A group¹³ recently claimed enthusiastically that vitrectomy with branch retinal vein cannulation and infusion of t-PA in CRVO resulted in visual recovery which was “much better than what occurs as part of the natural history of CRVO”. However, a critical review of that study reveals that the mode of treatment has no scientific rationale and that their claims are unwarranted. I have discussed the reasons for this at length elsewhere¹⁴. The claim of a result "much better than what occurs as part of the natural history of CRVO" was based on their comparison of visual acuity in their study with my natural history study findings.¹⁰ They stated: "In the study by Hayreh only 123 of 544 eyes with non-ischemic CRVO (23%) recovered vision to a level of at least 20/200". It mystifies me where they got their numbers of "123 of 544 eyes" in my paper¹⁰ and how they came up with their interpretation. It is clear they misunderstood the visual acuity data in my paper (see Table 2 above)¹⁰. My natural history study¹⁰ was based on 144 eyes with resolved non-ischemic CRVO (NOT 544 ) and it showed that in them the final visual acuity on resolution of CRVO was 20/40 or better in 65%, and it was better than 20/80 in 74%. When I¹⁴ challenged that misquotation, they¹⁵ offered a totally invalid, distorted interpretation of results of my study. In fact, their entire response to the various issues raised in my comments had little logic.¹⁵
  
  In addition, there is a considerable problem with the safety of the procedure. The authors claimed that it “is a relatively safe procedure” but their data shows that the extent of complications reported by the authors is so high as to be totally unacceptable.¹⁴
  
  Conclusion: In spite of various claims made in various studies about the beneficial effect of thrombolytic therapy in CRVO, there is little scientifically valid evidence of its effectiveness for several reasons. This is particularly so since the thrombus organizes within few days and new capillaries and fibroblasts grow in from the vessel wall to convert it into vascular connective tissue which cannot be dissolved by thrombolytic agents given by any route by the time most CRVO patients come for consultation. Moreover, thrombolytic therapy has serious ocular and even fatal systemic side-effects.
  
  
• Surgical decompression of CRV: I have recently discussed in detail the problems and dangers of this surgical procedure.⁶ This procedures is of NO scientific merit at all, and could be dangerous. Of particular concern in this context is the recent claim by Opremcak et al.¹⁶ about surgical decompression of the CRVO by a procedure they called “radial optic neurotomy”. They made a radial cut from the vitreous side in the optic nerve head, extending all the way down to the lamina cribrosa, adjacent sclera and cutting the arterial circle of Zinn and Haller. They claimed that “radial optic neurotomy” is a “surgically feasible and safe procedure” and is “beneficial”. I have researched various basic and clinical aspects of the optic nerve head and CRVO since 1955.¹⁷ Based on that, I find that this procedure lacks any scientific rationale, could be harmful, and comes without reliable evidence that it has any beneficial effect. I have discussed at length elsewhere the various problems with this procedure and their claims.¹⁷
  
  Conclusion: The whole idea of surgical decompression of central retinal vein in CRVO is ill-conceived and based on lack of basic understanding of: (a) the anatomy of the optic nerve and CRV and their relationship with each other, (b) the site of thrombosis in central retinal vein, and (c) the fact that a vein completely closed by a thrombus cannot be opened by “decompression” because the thrombus organizes shortly after it is formed (see above). Above all, it is a dangerous procedure.
  
  
• Laser-induced chorioretinal venous anastomosis for treatment of non-ischemic CRVO: This is one of the treatment modalities being advocated for nonischemic CRVO. To evaluate the role of these iatrogenic chorioretinal anastomoses in the management of CRVO, let us review the available information on it. McAllister and Constable¹⁸, in 1995 first reported producing chorioretinal anastomoses experimentally in eyes with nonischemic CRVO by using high power density argon laser photocoagulation to one of the retinal veins in the lower part of the fundus at least 3 disc diameter away form the optic disc. Based on their studies, they advocated laser-induced chorioretinal anastomosis as a treatment modality for nonischemic CRVO. In order to judge the appropriateness of this mode of treatment, one has to evaluate its benefits and risks from the available data.
  
  Visual outcome: There are only two series with any appreciable number of cases reported so far. McAllister and Constable¹⁸ in their original study in eyes with nonischemic CRVO, were able to produce successful chorioretinal anastomoses in only 8 of 24 eyes (33%) in 3 to 7 weeks, after 1 to 5 laser attempts. Among the 8 eyes with successful anastomosis, 6 eyes with initial visual acuity of about 20/200 had final visual acuity of 20/200 in 2, 20/120 in one, 20/60 in 2, 20/20 in one; and 2 eyes with initial visual acuity of 20/120 improved to 20/30. Fekrat et al.,¹⁹ successfully produced the anastomosis in 9 of 24 (38%) eyes with nonischemic CRVO, within 8 weeks after the laser application. Six of the 9 eyes in this series already had developed retinociliary collaterals on the optic disc before the laser procedure was performed so that nature had already performed what this iatrogenic procedure was meant to do. Browning and Antoszyk²⁰ tried laser-induced anastomosis in 8 eyes with nonischemic CRVO (successful anastomosis developed in only 2 eyes), and reported visual acuity improvement in 2 independent of failed attempts at anastomosis creation and did not improve or worsened in 6 eyes, including the 2 with the successfully created anastomosis. The conventional "two or more line" improvement in visual acuity occurred in 5 of 8 (62.5%) eyes of McAllister and Constable¹⁸ and in 3 of 9 (33%) eyes of Fekrat et al.,¹⁹ with no significant improvement in the rest. The authors of these two latter series claimed that none of the eyes with successful anastomosis progressed to ischemic CRVO.
  
  Complications: Various studies have reported a number of complications which can be divided into immediate and late complications.
  1. Immediate complications: Among the immediate complications noticed at the time of laser application, those reported by McAllister and Constable¹⁸ included hemorrhages from the retinal vein (in 40%), subretinal hemorrhages (in 7%), and choroidal hemorrhages (in 5%). Fekrat et al.¹⁹ reported transient vitreous hemorrhage at the time of laser application in 42%. In my studies, producing experimental branch retinal vein occlusion by argon laser application in rhesus monkeys in the 1970s, I found that retinal, subretinal, choroidal and vitreous hemorrhages commonly developed at the time of laser application.
  2. Late complications: McAllister and Constable¹⁸ reported branch retinal vein occlusion with segmental retinal ischemia (in 11%), preretinal (in 13%) and subretinal (in 5%) fibrosis at the site of the laser application, and development of preretinal neovascular frond over the site of laser application. Fekrat et al.¹⁹ reported localized choroidal neovascularization in 21%, mild preretinal fibrosis in 8%, and preretinal fibrosis and traction retinal detachment requiring vitrectomy in 4%. However, the authors claimed that there were no permanent vision-limiting complications. By contrast, Browning and Antoszyke²⁰ attempted to produce laser-induced venous anastomosis in 8 eyes with nonischemic CRVO (with 20 attempts they had 2 successful anastomoses but not of a therapeutic type), and of those 8 eyes, 3 developed iris neovascularization, retinal neovascularization at the laser site and vitreous hemorrhage, 2 developed traction retinal detachment, and one neovascular glaucoma. These eyes required secondary panretinal photocoagulation (in 3), pars plana vitrectomy (in one) and glaucoma seton implant (in one). They concluded that laser-induced chorioretinal anastomosis for nonischemic CRVO has greater risk and less success than the initial reports suggested, and that successful chorioretinal anastomosis does not preclude development of anterior segment neovascularization. In addition to these reports, during 1996-98, there are 4 more published reports of serious complications with this procedure; the reported complications include choroidal neovascular frond into the vitreous followed by vitreous hemorrhage, recurrent vitreous hemorrhage, deep subretinal hemorrhage, subretinal choroidal neovascular membrane, massive preretinal fibrosis, traction retinal detachment, and neovascular glaucoma. All these late complications were reported usually within the first few months after the procedure. The possibility of still more long-term complications cannot be ruled out.

  To place the value of laser-induced chorioretinal venous anastomosis for treatment of nonischemic CRVO in true perspective, one has to consider the natural history of nonischemic CRVO (see “Natural history of CRVO” above) .

  When evaluating the validity of claims of improved visual acuity in any study in the literature, one has to be aware of the possibility that apparent "improvement" in visual acuity can simply be the result of multiple artifacts in visual acuity testing (which is often done by technicians). In my experience of repeated testing of visual acuity, myself, in about three thousand patients with various circulatory disorders of the eye (e.g., anterior ischemic optic neuropathy, central and branch retinal artery occlusion and central and branch retinal vein occlusion, ocular ischemia) over time, I have found that the most important factor in apparent "improvement" of visual acuity may simply be a patient’s improved skill in reading the visual acuity chart; he/she may have learned by experience to read the test chart better by looking around and fixating eccentrically. This applies particularly to an eye which has a visual field defect or a scotoma passing through or just involving the central fixation spot. (Eyes with nonischemic CRVO invariably have poor visual acuity due to central scotoma.) That is why reports of improved visual acuity without corresponding improvement of central visual field defects can be misleading.²¹ None of the studies reported concurrent improvement of visual acuity and visual field.

  It is therefore evident from the available data that the visual outcome apparently achieved in eyes with nonischemic CRVO by laser-induced chorioretinal venous anastomosis seems no better, if not worse, than the natural history of the disease. On the top of that, the procedure is associated with a fairly high risk of serious vision threatening complications, not seen in non-ischemic CRVO.

  Conclusion: It is evident that the complications of laser-induced chorioretinal venous anastomosis for treatment of non-ischemic CRVO heavily outweigh any dubious benefits, and that this is not a safe and effective mode of treatment for a condition which has a fairly good outcome if simply left alone (see “Natural history of CRVO” above).