Pedro F. Lopez

Pathologic Features of Surgically Excised Subretinal Neovascular Membranes in Age-related Macular Degeneration

The histopathologic features of ten consecutive surgically excised subfoveal neovascular membranes from patients with age-related macular degeneration were examined. Ultrastructural features included the following in decreasing order of frequency: endothelium-lined vascular channels, new collagen, fibrocytes, retinal pigment epithelium, erythrocytes, and myofibroblasts. Chronic inflammatory cells were frequently evident and included macrophages, lymphocytes, and plasma cells. Basal laminar deposit or diffuse drusen were observed in six of the membranes. Photoreceptors and Bruchs membrane were each observed in three of the specimens, but were not associated with decreased postoperative visual acuity. Fibrin was observed in eight membranes, either within the stroma of the membrane or in association with subretinal hemorrhage.

Immunohistochemical and Histochemical Properties of Surgically Excised Subretinal Neovascular Membranes in Age-related Macular Degeneration

The immunohistochemical and histochemical properties of 16 surgically excised subretinal neovascular membranes from 16 patients with age-related macular degeneration were studied. Primary antisera to c-retinaldehyde-binding protein; leukocyte common antigen; factor VIII-related antigen; S-100 protein; glial fibrillary acid protein; muscle-specific actin; neuron-specific enolase; collagen types I, II, III, IV, and V; laminin; and fibronectin were used for immunohistochemical characterization of the membranes. Histochemical staining for lipid and mucopolysaccharide was performed. The results of the staining in conjunction with histologic examination showed the cellular components of the membranes to be composed of retinal pigment epithelium, inflammatory cells, vascular endothelium, glial cells, myofibroblasts, photoreceptor cells, and fibrocytes. The extracellular matrix of the membranes contained collagen types I, III, IV, and V; fibronectin; laminin; mucopolysaccharide; and lipid. These findings are consistent with the concept that subretinal neovascular membranes in age-related macular degeneration are composed of localized intra-Bruchs membrane granulation tissue proliferation associated with diffuse drusen.

Diode-laser Photocoagulation for Zone 1 Threshold Retinopathy of Prematurity

We used the diode-laser indirect ophthalmoscope in the treatment of 17 (30 eyes) infants with zone 1 (a circle centered on the optic disk with a radius of twice the distance from the disk to the fovea) threshold retinopathy of prematurity (at least five continuous or eight cumulative 30-degree sectors [clock hours] of ridge with extraretinal fibrovascular proliferation in the presence of plus disease). Mean follow-up was 31.2 weeks. Two eyes (6.7%) required retreatment of missed areas that had persistent plus disease (enlarged posterior veins and tortuous arterioles). A favorable outcome was attained in 25 eyes (83.3%). Five eyes (16.7%) developed retinal detachments, three of which remained stable at Stage 4A (extrafoveal retinal detachment) and two of which ultimately progressed to Stage 5 (total retinal detachment). Both eyes that went on to Stage 5 had severe posterior pole hemorrhages at the time of treatment. Two eyes that developed retinal detachments (one, stage 4A and one, stage 5) had rhegmatogenous components. Among 14 infants followed up for more than three months, four developed nystagmus, and six developed strabismus. In contrast to cryoablation, diode-laser photoablation of the peripheral retina was found to be an effective treatment for threshold retinopathy of prematurity located in zone 1. Portability and ease of use of the laser system, precision of treatment, and minimal postprocedural adnexal inflammation are further advantages of this therapeutic modality.

Autosomal-dominant Fundus Flavimaculatus: Clinicopathologic Correlation

The authors report the first clinicopathologic study of autosomal-dominant fundus flavimaculatus with late-onset atrophic macular degeneration in a 62-year-old man. Results of histopathologic examination disclosed the retinal pigment epithelium (RPE) to be distended by a periodic acid-Schiff (PAS)-positive, acid mucopolysaccharide-negative material. Transmission electron microscopy showed marked accumulation of lipofuscin and melanolipofuscin granules within the RPE. The different modes of genetic transmission and ultrastructural heterogeneity suggest that fundus flavimaculatus is a clinical syndrome representing several genetically and mechanistically distinct disorders whose common end-stage is a topographically similar accumulation of lipofuscin.

Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes. Submacular Surgery Trials Pilot Study report number 1

PURPOSE To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Well-defined subfoveal choroidal neovascular membranes in age-related macular degeneration.

PURPOSE The purpose of this study is to correlate the clinical, angiographic and ultrastructural features of well-defined subfoveal neovascular membranes. METHODS Fundus photographs and fluorescein angiograms of five well-defined subfoveal neovascular membranes associated with age-related macular degeneration and exudative retinal detachment were obtained. The subfoveal membranes were surgically excised via the pars plana. The center and peripheral portions of each membrane were evaluated by transmission electron microscopy for cellular and extracellular constituents. RESULTS Each subretinal neovascular membrane was composed of two distinct regions demonstrated by fluorescein angiography. The first component, the core, contained a brighter central area of hyperfluorescent leakage surrounded by a partial or complete cuff of elevated blocked choroidal fluorescence. Results of ultrastructural examination showed that the core was composed of a fibrovascular membrane characterized by endothelium-lined vascular channels with associated retinal pigment epithelium. The second region of the membrane, the rim, is previously unreported and is described in detail. It appeared as a minimally elevated, smooth, subretinal annular rim of hyperfluorescent staining that surrounded the core and was composed of fibrin, photoreceptor outer segments, and macrophages. CONCLUSIONS Well-defined subfoveal neovascular membranes can be appreciated with fluorescein angiography and are composed of a central core of subfoveal choroidal neovascularization surrounded by a peripheral rim composed of fibrin, photoreceptor outer segments, and macrophages.

Bone Marrow Transplant Retinopathy

Five of eight patients (62%) who survived at least six months after autologous or allogeneic bone marrow transplantation for acute leukemia developed occlusive microvascular retinopathy. Treatable retinal microangiopathy included a high incidence (80%) of clinically significant macular edema and one case of proliferative retinopathy with subhyaloid hemorrhage. The bone marrow transplant protocol required high-dose cytarabine hydrochloride and 1,200 cGy of total body irradiation. The development of radiation retinopathy after such low doses of teletherapy suggests that high-dose chemotherapy may increase the susceptibility for the development of retinopathy at otherwise safe radiation doses.

Topographic analysis and visual acuity after radial keratotomy.

Using a computerized corneal topographic mapping system that allows detailed examination of the corneal curvature in the vicinity of the visual axis, we identified separate regions of differing corneal curvature in three of 11 eyes after radial keratotomy. In these eyes, the excellent uncorrected visual acuity appeared to be inconsistent with the postoperative spherical equivalent as determined by refraction and corneal curvature by standard keratometer measurements. The distinct regions of corneal curvature appeared to serve as alternative effective optical zones, thus allowing the patients to have excellent visual acuity. In essence, the cornea became a multifocal lens. Although degradation in the contrast of the image as well as monocular diplopia are possible, our patients had no significant complaints.

Accidental Nd:YAG laser injuries to the macula

PURPOSE To study the clinical course of accidental, single-focus Nd:YAG laser injuries to the macula. METHODS We reviewed the clinical course of five eyes (four patients) that sustained macular injuries from a Nd:YAG laser. All patients were examined within 24 hours of injury and were observed without surgical intervention for a mean of 20 months (range, 12 to 32 months). RESULTS A single full-thickness foveal or parafoveal retinal hole was apparent in all eyes either on initial examination or within two weeks of injury. All macular holes were within 650 microns of the foveal center. The mean final visual acuity was 20/60 (range, 20/25 to 20/400) and was related to the distance between the macular hole and the foveal center. None of the eyes developed either subretinal neovascularization or clinically significant epiretinal membrane formation during the study period. CONCLUSIONS Despite initial poor visual acuity in patients who had a full-thickness foveal or parafoveal retinal hole, visual acuity improved without treatment when the site of the laser injury was located outside the foveal center.

Vitrectomy update for macular traction in ocular toxocariasis.

Purpose: To study the results of modern vitrectomy in traction and combined traction‐rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. Methods: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid‐gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. Results: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow‐up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. Conclusion: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.