Hilel Lewis

Vitrectomy for Diabetic Macular Traction and Edema Associated with Posterior Hyaloidal Traction

Pars plana vitrectomy with separation of the posterior hyaloid was performed in 10 eyes with diabetic macular edema and traction associated with a thickened and taut premacular posterior hyaloid. Nine of the 10 eyes had previous macular photocoagulation. Preoperative fluorescein angiography showed a deep and diffuse pattern of leakage in the macula. Intraoperatively, the attached and thickened posterior hyaloid was lifted and separated from the retina. Postoperatively, vision improved in nine eyes. The macular traction and edema resolved in eight eyes and decreased in two. Complications included a vitreous hemorrhage, a rhegmatogenous retinal detachment, cataract formation, and a mild epimacular membrane, each occurring in one eye. Vitreous surgery can improve the visual prognosis of some eyes with diabetic macular traction and edema associated with a thickened and taut posterior hyaloid.

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-Year results of a randomized clinical trial - VIP report no. 3

PURPOSE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Results and Prognostic Factors in Penetrating Ocular Injuries with Retained Intraocular Foreign Bodies

Of 105 eyes with ocular injuries involving retained intraocular foreign bodies, 63 (60%) had a final visual acuity of 20/40 or better; 20 (19%) were 20/50 to 5/200; and 15 (14%) were worse than 5/200. Six eyes (6%) were enucleated. The extent of visual recovery was limited in selected cases by the characteristics of the initial injury. Multivariate analysis was used to identify prognostic factors. Predictive of a good visual outcome (greater than or equal to 20/40) were: (1) initial visual acuity better than 20/40 and (2) the need for only one or two operations in the treatment of the injury. Predictive of a poor visual outcome (less than 5/200) were: (1) initial visual acuity worse than 5/200 and (2) a wound 4 mm or longer in length, independent of wound location. The visual outcome in this series of patients was compared with other large series of intraocular foreign bodies reported before the development of vitreous microsurgical techniques. The percentage of patients with a visual outcome of 20/40 or better has remained the same, whereas the incidence of enucleation has diminished.

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials--TAP Report no. 5

OBJECTIVE To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV). DESIGN AND SETTING Open-label extension of selected patients from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials, the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation, at 22 ophthalmology practices in Europe and North America. PARTICIPANTS Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss. METHODS Before receiving verteporfin therapy in the extension, eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards. Methods were similar to those described for 1- and 2-year results, with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions, including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment. RESULTS Of 402 patients in the verteporfin group, 351 (87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the extension study. The enrolled participants included 124 (78.0%) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline, of whom 105 (84.7%) completed the month 36 examination. Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study, with or without a month 36 examination, appeared more likely to have a younger age, better level of visual acuity, absence of fluorescein leakage from classic CNV, or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension. For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination, an average of 1.3 treatments were given from the month 24 examination up to, but not including, the month 36 examination. A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients at the month 36 examination. Visual acuity changed little from the month 24 examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for these eyes. Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36. Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension. One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension. CONCLUSIONS Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36, although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination. From these results, the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin. Additional treatment was judged likely to reduce the risk of further vision loss. Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension.

Intraoperative fibrinolysis of submacular hemorrhage with tissue plasminogen activator and surgical drainage.

Purpose This pilot study determined the safety and efficacy of intraoperative pharmacologie lysis of recent submacular hemorrhage with tissue plasminogen activator followed by surgical drainage of the unclotted blood in patients with age-related macular degeneration. Methods In a prospective study, 24 consecutive eyes with recent ( Results Twenty eyes (83%) had improved visual acuity after surgery, and eight eyes (33%) attained visual acuity of 20/200 or better. In a subset of 16 eyes with submacular hemorrhage of seven days duration or less, eight (50%) attained visual acuity of 20/200 or better. Factors associated with poor visual outcome included submacular hemorrhage with duration greater than seven days (P Conclusions Tissue plasminogen activator thrombolysis may be a valuable adjunct to the surgical treatment of select patients with sub-macular hemorrhages secondary to agerelated macular degeneration.

Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction

PURPOSE To review the clinical, photographic, fluorescein angiographic, and optical coherence tomographic findings in patients with the diabetic macular traction and edema (DMTE) associated with posterior hyaloidal traction (PHT). METHODS We performed a prospective review of nine eyes of nine patients with diabetic macular edema (DME) and PHT on clinical examination. The patients had a comprehensive ophthalmic history and examination, color photographs, fluorescein angiography, and optical coherence tomography (OCT). RESULTS All patients had diabetic retinopathy and DME. Of the nine eyes, eight patients had previous focal or grid photocoagulation. All nine eyes had a thickened, taut, glistening posterior hyaloid on clinical biomicroscopic examination with no posterior vitreous separation. Fluorescein angiography was performed on seven eyes, and all had early hyperfluorescence with deep, diffuse, late leakage in the macular area consistent with DMTE associated with PHT. Optical coherence tomography scans of the macular region revealed retinal thickening in all eyes with a mean retinal thickness of 556.9 +/- 114.7 microns. In addition, eight of the nine eyes had a shallow macular traction detachment associated with PHT. CONCLUSION Eyes with DME associated with PHT may have a shallow, subclinical, macular detachment. Optical coherence tomography may be useful in evaluating patients with DME to see if a macular detachment is present.

Decrease in the Risk of Bilateral Acute Retinal Necrosis by Acyclovir Therapy

We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis.

Macular translocation for subfoveal choroidal neovascularization in age- related macular degeneration: A prospective study

PURPOSE To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.

A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits.

PURPOSE Intravitreal injections of tissue plasminogen activator have been used to lyse fibrin from blood in the subretinal space, despite the lack of proof that tissue plasminogen activator can diffuse across the retina. We tested whether tissue plasminogen activator injected into the vitreous could penetrate the neural retina and enter the subretinal space. METHODS We injected a mixture of 50 microg of tissue plasminogen activator (70 kD) labeled with fluorescein isothiocyanate and rhodamine B isothiocyanate-labeled dextran, which has a lower molecular weight (20 kD), into the midvitreous cavity of one eye in each of 18 rabbits. The eyes were enucleated after 3, 6, and 24 hours, and cryosections were examined with epifluorescent microscopy to determine the distribution of the labeled molecules. We also evaluated tissue plasminogen activator pharmacokinetics in one eye each of 18 rabbits in which a subretinal clot was induced by injecting autologous blood (50 microL) into the subretinal space through the sclera. Fluorescein isothiocyanate-labeled tissue plasminogen activator was injected into the vitreous 2 days after induction of the subretinal clot. RESULTS Fluorescein isothiocyanate-labeled tissue plasminogen activator was present at the vitreal surface of the retina in a linear array in all 36 eyes studied, whereas the rhodamine B isothiocyanate-labeled dextran had diffused throughout the neural retina in the same sections. No fluorescein isothiocyanate signal was observed in the neural retina or in the subretinal clot. Vitreous hemorrhage caused by retinal perforation was observed in all eyes with intraretinal hemorrhage in which fluorescein isothiocyanate fluorescence was seen in the neural retina and inside the clot. CONCLUSION Intravitreal tissue plasminogen activator did not diffuse through the intact neural retina to reach a subretinal clot. This study demonstrates no scientific rationale for the intravitreal tissue plasminogen activator treatment of submacular hemorrhage without vitreous hemorrhage presumably caused by an overlying retinal break.

Development of a multiple-drug delivery implant for intraocular management of proliferative vitreoretinopathy

A prototype multiple-drug delivery implant has been developed for the intraocular management of proliferative vitreoretinopathy (PVR). Because of the recurrent nature of the disease, PVR causes blindness in approximately 7% of patients who have undergone retinal re-attachment surgery. The poly(dl-lactide-co-glycolide) 50/50 (PLGA) implant consists of three cylindrical segments, each of which contains one of the following drugs: 5-fluorouridine (5FUrd, an antimetabolite), triamcinolone (Triam, a corticosteroid), and human recombinant tissue plasminogen activator (t-PA, a thrombolytic agent). The device can be inserted through a 20-gauge syringe needle into the vitreous body of the eye. The implant also possesses a PLGA coating over the t-PA-containing terminal segment, which creates a lag-time to deliver t-PA when most needed and to decrease the risk of postoperative bleeding. Two methods of cylinder fabrication were investigated: heat and solvent extrusion. The release behavior of several drugs was examined as a function of the processing variables including: extrusion method, drug loading, polymer molecular weight, and drug particle size. The presence of either the organic solvent (acetone) during processing or a highly water-soluble drug (5FUrd) in the formulation increased the polymer porosity, which in turn, increased the drug release-rate. Drug loading effects were consistent with percolation concepts, and a low-molecular-weight PLGA (e.g., Mw=42000 for inherent viscosity=0.58 dl/g) was desirable to produce controlled release close to one month. Based on pharmacological and pharmacokinetic data of these compounds and our clinical experience with this disease, several design criteria for a combined implant were devised. Optimal cylindrical segments from the formulation studies were selected and combined in series to form a contiguous implant. After successful combination and coating procedures were developed, prototype implants were prepared. From the 3-drug prototype, 5FUrd and Triam were released approximately 1 microgram/day for over 4 weeks and 10-190 microgram/day over 2 weeks, respectively. The solvent-extrusion procedure did not significantly alter the stability of the encapsulated t-PA (>94+/-5% serine protease activity after preparation). After a lag-time of approximately 2 days, t-PA was released active at a rate of approximately 0.2-0.5 microgram/day in approximately 2 weeks. The release characteristics from the combined implant largely met our initial design criteria. Hence, controlled-release implants of this kind may have potential use for intraocular treatment of PVR.