Pars Plana Optic Disc Surgery for Central Retinal Vein Occlusion

SURGICAL TECHNIQUE Lamina Puncture Pars Plana Optic Disc Surgery for Central Retinal Vein Occlusion

Eugene S. Lit, MD; Miltiadis Tsilimbaris, MD; Eustratios Gotzaridis, MD; Donald J. D’Amico, MD

Objective: To determine the feasibility of creating a peri- Results: A lancet with a sharp cutting edge on one side vascular space adjacent to the central retinal vein at the and an opposing blunt edge is repeatedly able to create a level of the lamina cribrosa as a potential method of re- perivascular space with limited optic nerve fiber damage. establishing perfusion in central retinal vein occlusion. Conclusions: Lamina puncture is technically feasible, Methods: Various designs for a puncture instrument, and evaluation in carefully selected patients appears or lamina puncture lancet, were investigated in cadav- warranted. ers, pigs that had undergone enucleation, and in vivo rabbit eyes. Arch Ophthalmol. 2002;120:495-499

ENTRAL RETINAL vein oc- cribrosa predisposes this location to throm- clusion (CRVO) remains a bus formation. difficult and often frustrat- We postulated that it might be pos- ing disease for both the pa- sible to restore normal perfusion to the cen- tient and the ophthalmolo- tral retinal vein if a surgical technique could gist.C Although some younger patients with be developed to release the constriction of nonischemic forms may recover, most pa- the central retinal vein by the surrounding tients with CRVO are left with poor vision; connective tissue at the level of the lamina in patients with widespread capillary non- cribrosa. The resulting increase in luminal perfusion, less than 10% maintain a visual diameter of the central retinal vein might acuity better than 20/400 OU.1 No treat- allow the passage of a thrombus. Alterna- ment has proved useful in improving vi- tively, the increased intraluminal diameter sion, and ophthalmic care is supportive with might permit sufficient blood flow at the observation for the development of iris neo- level of the lamina cribrosa to allow for in- vascularization and the need for interven- creased perfusion of the retina, even if the tion with retinal ablation.2 thrombus was not dislodged or expressed Histological studies suggest that re- mechanically. gardless of the level of perfusion, most or We tried to determine the feasibility all cases of CRVO result from thrombus of transvitreal optic disc surgery to create formation in the central retinal vein at or a perivascular opening in the lamina just posterior to the lamina cribrosa.3 Ana- cribrosa, which we termed lamina punc- tomically, the luminal diameter of the cen- ture, as a prelude to considering such an tral retinal vein is narrowest at this level, intervention in patients with CRVO. resulting from the relatively denser connective tissue that makes up the lamina MATERIALS AND METHODS cribrosa encircling the retinal vessels. The development of CRVO is undoubtedly Initial experiments were performed on hu- multifactorial, including the resultant in- man cadaver eyes and enucleated pig eyes; creased turbulence in blood flow, pos- the latter were chosen for their anatomical sible concomitant endothelial cell dam- similarity to human eyes. Lamina punc- From the Retina Service of the age, and possible systemic factors, and ture was performed in enucleated eyes af- Massachusetts Eye & Ear results in a wide variety of CRVO forms ter removing the anterior segment, includ- Infirmary and the Department with variable degrees of perfusion. Nev- ing both the vitreous and the vitreous base. of Ophthalmology, Harvard ertheless, the mechanical constriction of This preparation permitted direct visual- Medical School, Boston, Mass. the central retinal vein at the lamina ization of the posterior eye cup and optic

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 their ductility, relative strength, and ability to be used in areas with small dimensions, all of which facilitated frequent early changes. Subsequent modifications were refined on instruments made of surgical stainless steel. Lamina puncture lancets were evaluated for each instrumental design on the basis of the following parameters: the ability to create a perivascular space around the central retinal vein, the presence and degree of damage to the vessel wall, the amount of residual connective tissue adjacent to the vessel wall, and the amount of damage done to nerve fibers.

RESULTS Figure 1. The optic nerve in an enucleated pig eye after lamina puncture using a blunt lancet. The vessel wall remains intact, but there is significant collateral damage to the adjacent neural tissue (hematoxylin-eosin; original magnification ϫ 20). Initial experiments on enucleated eyes were encouraging because the vessel wall of the central retinal vein appeared to be much stronger than the connective tissue fibers of the lamina cribrosa, and consequently it was possible to selectively dis- rupt the lamina cribrosa without vio- lating the integrity of the central retinal vein. Although blunt lamina puncture lancets in combination with multiple passes and a slightly roughened surface were very effec- tive in stripping away connective tissue from around the central retinal vein, these instruments caused significant collateral damage to the optic nerve fiber tissue (Figure 1). Puncture instruments with a sharp cutting edge were superior to blunt instruments in minimizing the area of damage to optic nerve fibers, but Figure 2. The optic nerve in an enucleated pig eye after lamina puncture using a sharp lancet. Although there is little damage to the adjacent neural tissue, the vessel wall integrity has been violated this cutting edge created damage in (hematoxylin-eosin; original magnification ϫ 20). the central retinal vein wall if directed against the vessel (Figure 2). disc using a dissecting microscope. cet was introduced through this scle- As a result, puncture instru- Subsequent experiments used intact rotomy without removal of the vitre- ments were created that combined Dutch-belted rabbits in a transvit- ous. A contact lens and operating a slightly roughened blunt side with real approach. These experiments microscope were used for visualiza- a cutting edge on the opposite side. were reviewed and approved by the tion and illumination. The various These lancets were passed through animal review committee at our hos- lancets were moved across the vitre- the optic nerve head with the cut- pital. After anesthesia with 3 to 5 mL ous and into the optic disc. The rab- ting edge directed away from the ves- of a mixture (1:1) of intramuscular bits were euthanized, and the eyes sel wall. This design required little ketamine hydrochloride (100 mg/ were enucleated after 3 to 4 minutes force to allow a relatively small punc- mL) and xylazine hydrochloride (20 of observation for hemorrhage and ture to be made through the lamina mg/mL), the animals were placed un- confirmation of retinal vascular per- cribrosa, especially when the instru- der a dissecting microscope, and ad- fusion. All tissues were processed for ment was angled so that the cutting equate anesthesia was confirmed. Fol- light microscopy using conven- edge entered the nerve head first. At lowing a localized peritomy, a 1.5-mm tional techniques. the same time, the roughened blunt superior sclerotomy was performed The instruments were initially side did not damage the vein wall approximately 1.5 mm posterior to shaped from copper and molten glass. and was able to completely strip the limbus. The lamina puncture lan- These 2 materials were selected for away the connective tissue of the

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 lamina cribrosa from the vessel wall with only a few consecutive passes. This final version was 300 to 400 µm in width, with a sharp portion about 60 µm in length and a relatively blunt tip (Figure 3). The shaft diameter was equivalent to 20 gauge, allowing it to be passed through a standard sclerotomy. Small (300- to 400-µm diameter) puncture wounds were achievable immediately adjacent to the vessel walls, with no wall damage and minimal optic nerve fiber damage (Figure 4). This final lancet design was then used to create lamina punctures in 8 consecutive in vivo rabbit eyes. In 7 of the 8, there was no bleeding and grossly normal perfusion after the puncture. The vein wall was intact on Figure 3. The optic nerve in an enucleated pig eye after lamina puncture using the final instrument histological examination in all cases design. There is little damage to the adjacent neural tissue, and the vessel wall integrity is maintained (hematoxylin-eosin; original magnification ϫ 20). (Figure 5). In the sole eye in which there was bleeding, the amount of blood was minimal, and hemostasis occurred spontaneously after about 20 seconds. Although the central retinal vein was intact on histological examination, a small branching vessel Fine, Noncutting Tip on the optic disc had been severed, Burnished, accounting for the hemorrhage. Noncutting Edge Sharp Edge

COMMENT

Although many questions may be raised about the possibility of effec- tive therapy for an acutely compro- mising event such as CRVO, the development of a thrombus at the site of constriction by the lamina cribrosa appears central to this disease. Con- sequently, attempts to relieve vascular compromise and restore blood Figure 4. The final instrument design: the lance tip is blunt, and the surface facing the vessel wall is blunt flow are consistent with the under- and slightly roughened. The opposite edge is sharp, reducing the amount of neural tissue damage caused during tissue entry. The sharp edge flares out slightly to a blunt surface and pushes neural tissue aside, lying pathophysiologic characteris- further minimizing collateral damage. tics of CRVO. Lamina puncture may relieve constriction on the central retinal vein and permit thrombus mi- and the possibility of excessive col- nerve head trauma would not be a gration or bypass by creating a po- lateral optic nerve damage. The lat- significant limiting factor in the ini- tentially enlarged vascular diam- ter seems unlikely, however, given tial evaluation of the procedure. Un- eter. Furthermore, it is also possible the anatomy of the optic nerve head. til further in vivo experiments are that mechanical compression of the Macular fibers enter the optic nerve performed, it is not possible to de- vein during the procedure might re- head along the periphery. With the termine if releasing constriction of sult in clot dislodgment unrelated to puncture adjacent to the central reti- the central retinal vein at the level vascular diameter, but this mecha- nal vein and with damage therefore of the lamina cribrosa will allow for nism cannot be evaluated from the limited to the central portion of the mobilization of the thrombus and available animal models. nerve, it seems reasonable that any reperfusion of the retina. In addition to other concerns reduction in central vision associ- There have been many previ- regarding the visual efficacy of re- ated with the puncture would be ous attempts to develop treatments for establishing blood flow by any minimal. Furthermore, for CRVO in CRVO. Early approaches such as the means, 2 potential limitations to patients older than 65 years, the ex- use of cholesterol-lowering agents4 or lamina puncture are the failure of the tremely poor natural history for vi- x-rays5 did not take into account the technique to reestablish perfusion sual recovery suggests that optic cause of the disease; namely, the for-

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 blood flow, this therapeutic strategy does not relieve the constriction of the central retinal vein at the level of the lamina cribrosa. In addition, endothelial cell proliferation following ve- nipuncture may further limit lumen size if constriction around the vessel is not relieved. Nevertheless, the results of current clinical trials may demonstrate the efficacy of pharmacologic clot lysis. It may be of inter- est to explore the combination of lo- cal delivery of a thrombolytic agent with lamina puncture, as both are directed at the same pathophysiologic dysfunction. E. Mitchel Opremcak, MD (oral communication, May 2001), has performed a similar maneuver us- Figure 5. The optic nerve in an in vivo rabbit eye after lamina puncture using the final instrument design. ing an unmodified microvitreoreti- There is little collateral tissue damage with an intact vessel wall (hematoxylin-eosin; original magnification ϫ 20). nal blade and cutting part of the optic nerve near the central retinal vein as well as the adjacent peripapil- mation of a thrombus at the level of encouraging for our current study. It lary sclera and retina. In his tech- the lamina cribrosa. More recent ap- suggests that if lamina puncture is nique, a single radial incision is made proaches have been based on this successful in improving retinal ve- using a microvitreoretinal blade fol- pathogenesis. nous outflow, there is the potential for lowing vitrectomy. He reports that Rather than reperfusion of the visual improvement. he has operated on more than 40 pa- retina via the central retinal vein, Mc- Thrombolytic agents are also tients using this technique, with an Allister, Vijayasekaran, et al,6-8 cre- used to dissolve a thrombus at the increase in perfusion of the central ated a new venous outflow route by level of the lamina cribrosa. Early retinal vein in most patients and no forming a chorioretinal venous anas- studies using systemic streptoki- cases of significant visual loss. His tomosis through the use of high- nase9 showed statistically improved method appears very similar to our energy argon lasers. They showed the vision in patients who were taking the earlier techniques in which a sharp feasibility of such anastomosis in both drug. However, in 3 of 20 patients, se- instrument was used, and for the rea- dog and rat models. McAllister and vere vitreous hemorrhage occurred sons stated previously, we believe colleagues showed that similar cho- leading to functional blindness. A that our final instrument design may rioretinal venous anastomosis could more recent study used tissue-type result in less hemorrhage. Never- be created in 8 of 24 patients in a small plaminogen activator (tPA), which theless, it is encouraging that in his pilot study. Encouragingly, in those has a better safety profile than strep- group of patients, no significant vi- 8 patients, not only was retrograde ve- tokinase, has a shorter circulating sual loss occurred. nous flow demonstrated with some half-life, is less antigenic, and carries The idea of cutting the sclera degree of visual improvement, but the less risk of creating a fibrinolytic state surrounding the optic nerve was first anastomosis seemed to remain patent leading to significant systemic hem- proposed by Vasco-Posada,12 al- for the duration of the study, rang- orrhage. A pilot study using tPA by though he did not have access to ing from 1 to 3 years. Although ap- Elman10 in 1996 had encouraging re- modern vitrectomy techniques and proximately 40% of the sites with at- sults. Fifty-nine percent of the 89 pa- used an external approach. Al- tempts at anastomosis creation tients with sufficient follow-up (of an though one other study13 reports us- developed hemorrhages, these were original 96 patients) had 3 or more ing this technique, the external ap- all visually insignificant and re- lines of visual improvement. How- proach was not further developed. solved spontaneously. Nevertheless, ever, 3 patients developed intraocu- Because subsequent histopatho- the potential for a significant hemor- lar bleeding, and 1 patient had a fa- logic studies have localized the rhage exists, as does the develop- tal hemorrhagic stroke. A decreased thrombus to the level of the lamina ment of preretinal and subretinal fi- risk of extraocular hemorrhage might cribrosa, an internal approach that brosis. A larger multicenter trial is be achieved with localized delivery of can reach the proper anatomical level under way to determine the efficacy tPA via retinal vein cannulation. seems more direct. of this treatment. The fact that the lim- Weiss11 showed that this is techni- Surgery to enlarge the perivas- ited reperfusion achieved in the 33% cally feasible and was able to achieve cular tissue in the lamina cribrosa via of patients in whom an anastomosis modest improvement in 4 of 8 eyes, a pars plana approach is techni- could be successfully created was as- with no catastrophic adverse effects. cally feasible and potentially appli- sociated with visual improvement, Although pharmacologic disso- cable to patients with CRVO. A lan- whereas not statistically significant, is lution of a thrombus may restore cet with a sharp cutting edge on one

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 side and a roughened blunt side sachusetts Eye & Ear Infirmary, 6. McAllister IL, Yu DY, Vijayasekaran S, Barry C, placed adjacent to the central reti- 243 Charles St, Boston, MA 02114 Constable I. Induced chorioretinal venous anastomosis in experimental retinal branch vein oc- nal vein was repeatedly able to pro- (e-mail: [email protected]). clusion. Br J Ophthalmol. 1992;76:615-620. duce a significant perivascular space 7. Vijayasekaran S, Yu DY, McAllister IL, Barry C, with limited collateral nerve fiber REFERENCES Constable I. Significance of Bruch’s membrane in damage. Although the potential ef- the creation of iatrogenic chorioretinal venous anastomosis. Curr Eye Res. 1994;13:29-33. ficacy and complications of this pro- 1. The Central Vein Occlusion Study Group. Base- 8. Vijayasekaran S, Yu DY, McAllister IL, Barry C, cedure in patients with CRVO are line and early natural history report: the Central Constable I. Optimal conditions required for the unknown, our study’s promising re- Vein Occlusion Study. Arch Ophthalmol. 1993; creation of an iatrogenic chorioretinal venous anas- sults and the dismal visual progno- 111:1087-1095. tomosis in the dog using argon green laser pho- sis in certain subgroups of patients 2. The Central Vein Occlusion Study Group. A ran- tocoagulation. Curr Eye Res. 1995;14:63-70. domized clinical trial of early panretinal photoco- 9. Kohner EM, Pettit JE, Hamilton AM, Bulpitt CJ, Dol- with CRVO suggest that lamina agulation for ischemic central vein occlusion: the lery CT. Streptokinase in central retinal vein oc- puncture should be evaluated in a Central Vein Occlusion Study Group N report. Oph- clusion: a controlled clinical trial. Br Med J. 1976; select group of patients. thalmology. 1995;102:1434-1444. 1:550-553. 3. Green WR, Chan CC, Hutchins GM, Terry JM. Cen- 10. Elman MJ. Thrombolytic therapy for central reti- tral retinal vein occlusion: a prospective histo- nal vein occlusion: results of a pilot study. Tr Am Submitted for publication October 11, logical study of 29 eyes in 28 cases. Trans Am Ophthalmol Soc. 1996;94:471-504. Ophthalmol Soc. 1981;89:371-422. 11. Weiss JN. Retinal surgery for treatment of cen- 2001; final revision received January 4. Clements DB, Elsby JM, Smith WD. Retinal vein tral retinal vein occlusion. Ophthalmic Surg La- 6, 2002; accepted January 18, 2002. occlusion: a cooperative study of factors affect- sers. 2000;31:162-165. Supported in part by the Vitreo- ing the prognosis, including a therapeutic trial of 12. Vasco-Posada J. Modification of the circulation retinal Research Fund (Dr D’Amico), Atromid S in this condition. Br J Ophthalmol. 1968; in the posterior pole of the eye. Ann Ophthalmol. 52:111-116. 1972;4:48-59. Boston, Mass. 5. Hesbery RJ. X-ray treatment of thrombosis of the 13. Arciniegas A. Treatment of the occlusion of the Corresponding author and re- retinal vein and several types of iridocyclitis. Am central retinal vein by section of the posterior ring. prints: Donald J. D’Amico, MD, Mas- J Ophthalmol. 1944;27:864-875. Ann Ophthalmol, 1984;16:1081-1086.

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