Robert N. Johnson

Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age

PURPOSE To investigate whether hypercoagulability plays a role in thrombus formation in patients with central retinal vein occlusion (CRVO) who are less than 56 years of age. DESIGN Prospective, observational case series with retrospective comparative controls. PARTICIPANTS AND CONTROLS Participants included 55 consecutive patients with CRVO less than 56 years of age. The laboratorys age-matched control groups were used to compare results for the same tests. METHODS Fifty-five patients with CRVO less than 56 years old (mean age, 44 years) underwent laboratory evaluation for homocysteine, activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies. The results were compared with previously drawn age-matched control groups obtained by the same laboratory for statistical significance. MAIN OUTCOME MEASURES Patients were considered to have a positive test if their results were outside the laboratorys established range. RESULTS Fifteen of 55 patients (27%) had one positive test result suggesting hypercoagulability. Compared with the control groups, these patients less than 56 years old with CRVO had a higher incidence of coagulation abnormalities by laboratory testing. Among the parameters tested, hyperhomocysteinemia and circulating antiphospholipid antibodies were significantly more common in the CRVO patients (P < 0.05) compared with age-matched controls. CONCLUSIONS Hypercoagulability may play a role in the pathogenesis of CRVO in patients less than 56 years old. The cause of CRVO remains multifactorial, and laboratory tests suggesting hypercoagulable states alone cannot account for the cause in most of these patients less than 56 years of age. The authors recommend examining blood pressure, intraocular pressure, complete blood count, glucose levels, and a lipid panel on all patients with CRVO. When tests for these common risk factors for CRVO are negative, consider ordering selected tests in young patients with CRVO to rule out thrombophilias, especially in patients with bilateral CRVO, a history of previous thrombosis, or family history of thrombosis.

Vitrectomy for Prevention of Macular Holes: Results of a Randomized Multicenter Clinical Trial

PURPOSE: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. METHODS: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. RESULTS: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation (P = 0.81). This difference of 3% has a 95% confidence interval of (-21%, 27%). CONCLUSION: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.Purpose: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. Methods: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. Results: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation ( P = 0.81). This difference of 3% has a 95% confidence interval of (-21%,27%). Conclusion: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.

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.

Traumatic macular hole: observations, pathogenesis, and results of vitrectomy surgery.

PURPOSE To review our experience with vitrectomy surgery techniques for the treatment of traumatic macular holes and the biomicroscopic and surgical findings. DESIGN Retrospective noncomparative, multicenter, case series. PARTICIPANTS AND INTERVENTION Twenty-five patients with traumatic macular hole underwent surgical repair. INTERVENTION Vitrectomy with membrane peeling and gas injection followed by prone positioning for 7 to 14 days. MAIN OUTCOME MEASURES Postoperative evaluation included visual acuity testing, closure of the macular hole, and ocular complications. RESULTS The macular hole was successfully closed in 24 of 25 cases (96%). The visual acuity improved two or more lines in 21 (84%) cases, and 16 (64%) achieved 20/50 or better vision. CONCLUSIONS Vitrectomy surgery can successfully close macular holes associated with trauma and improve vision.

CENTRAL RETINAL VEIN OCCLUSION IN YOUNG ADULTS (PAPILLOPHLEBITIS)

We performed a retrospective study of 103 cases of central retinal vein occlusion (CRVO) in young, nondiabetic adults that were followed for at least six months. Of these patients, 64% were men and 36% were women. While visual acuity was usually good, 33 eyes (32%) had a final visual acuity of 20/200 or worse, including 6 eyes (6%) with a final visual acuity of no light perception. Ocular complications included chronic cystoid macular edema, macular pigmentary changes (37%), sheathing of retinal vessels (22%), venous collaterals of the disc (33%), macular hole formation (1%), neovascularization of the disc (1%), retina (1%), and iris (19%), neovascular glaucoma (8%), and vitreous hemorrhage (7%).

Grid Laser Photocoagulation for Macular Edema in Bilateral Juxtafoveal Telangiectasis

OBJECTIVE The purpose of the study is to report the efficacy of laser photocoagulation treatment for macular edema in bilateral juxtafoveal telangiectasis (BJT). DESIGN The study design was a retrospective, clinical study. PARTICIPANTS The authors observed 14 patients with BJT, studying the visual acuities and retinal changes of treated and untreated eyes. MAIN OUTCOME MEASURES Visual acuity, presence of macular edema, and associated retinal findings were measured. RESULTS Of 28 eyes, 10 (8 patients) received 15 laser photocoagulation treatments for macular edema. Neither treated nor untreated eyes had visual improvement of two or more lines. After treatment, five eyes (50%) had increased retinal vascular distortion develop, three (30%) had new draining retinal venules, five (50%) had intraretinal fibrovascular tissues, and four (40%) had retinal and preretinal hemorrhages develop. CONCLUSIONS Grid laser photocoagulation therapy for macular edema in patients with BJT appears to neither improve nor stabilize long-term visual acuity. In addition, treatment is associated with retinal pigment epithelial changes, increased postoperative retinal vascular distortion, postoperative vascularized retinal scars, and postoperative retinal hemorrhages. These changes, however, do not appear to cause a further loss of vision.

Intravitreal Bevacizumab For Previously Treated Choroidal Neovascularization From Age-related Macular Degeneration

Purpose: To report the optical coherence tomography (OCT) findings and visual results in a series of patients treated with intravitreal bevacizumab for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), and to determine if a difference in treatment effect exists between previously treated and treatment naïve patients. Methods: A retrospective review of all patients treated with intravitreal bevacizumab for CNV from AMD with visual acuity greater than or equal to 20/320 between September 2005 and February 2006 was performed. OCT data recorded included central macular thickness and the presence or absence of cystic intraretinal fluid, subretinal fluid, or pigment epithelial detachment at the time of the initial injection, at 1-week, 1-month, and 3-month intervals, as well as at the end of follow-up. Visual acuity measurements were recorded using Early Treatment Diabetic Retinopathy Study charts. Any ocular or systemic adverse events were recorded. Statistical analysis was performed to determine if OCT and visual acuity results were significant and to determine if a difference in outcomes existed between previously treated patients and treatment naïve patients. Results: Fifty-four eyes of 51 patients treated with intravitreal bevacizumab for CNV from AMD were identified. A total of 178 injections were performed. Mean number of days of follow-up was 138 with 91% of patients having at least 90 days of follow-up. Seventy percent of patients had undergone previous treatment for CNV. The mean number of intravitreal bevacizumab injections per eye was 3.3. Combined treatment with photodynamic therapy was provided in 20% of cases at the initial intravitreal injection. OCT data for all patients revealed an initial mean thickness of 362 &mgr;m, which was decreased at 1 week to 278 &mgr;m (P = 0.001), 235 &mgr;m at 1 month (P < 0.0001), 238 &mgr;m at 3 months (P = 0.0004), and 244 &mgr;m for the end of follow-up (P < 0.0001). Cystic retinal edema, subretinal fluid, and pigment epithelial detachment resolved in the majority of cases, but pigment epithelial detachment frequently took longer to resolve. Initial mean visual acuity was 20/125 (logMAR 0.8), and final mean visual acuity was 20/100 (logMAR 0.7) (P = 0.03). There was no difference in OCT or visual acuity outcomes (P = 0.62 and P = 0.28, respectively) between previously treated and treatment naïve patients. There was no difference in OCT or visual acuity outcomes (P = 0.67 and P = 0.21, respectively) between patients who received combination therapy and those who received monotherapy with intravitreal bevacizumab. No systemic or ocular adverse events were recorded. Conclusion: Intravitreal bevacizumab for CNV from AMD results in a rapid decrease in OCT-measured retinal thickness in a majority of cases. Visual acuity also improved in this series, suggesting a potential corresponding visual benefit. This series suggests that previously treated and treatment naïve patients have similar outcomes.

Vitrectomy in Eyes with Peripheral Retinal Angioma Associated with Traction Macular Detachment

PURPOSE Peripheral angiomas have been associated with epiretinal membranes and traction retinal detachment. The authors investigated the timing, results, and complications of vitreous surgery to remove the retinal traction and treat the peripheral vascular tumor. METHODS The authors reviewed the results of ten eyes that had undergone vitrectomy for macular pucker and/or traction retinal detachment. These eyes had either preoperative or intraoperative treatment of the peripheral tumor. RESULTS Patients were followed 4 to 95 months. Six eyes had nonfamilial peripheral acquired retinal hemangioma, three had von Hippel angiomas, and one had multiple large peripheral retinal angiomas associated with extensive retinal telangiectasis. Four eyes received cryotherapy and/or laser photocoagulation 2 to 3 months before surgery. In the remaining six eyes, initial treatment to the peripheral angioma was performed at the time of vitreous surgery. At final follow-up, all eyes were attached without retinal traction. Vision improved in all eyes; six (60%) achieved 20/50 or better visual acuity. Complications included recurrent epiretinal membrane (n=3); nonregressed angiomas (n=3); increased nuclear sclerosis (n=2); and retinal detachment (n=1). CONCLUSION Vitreous surgery, when applied to epiretinal membranes or traction retinal detachments associated with peripheral vascular tumors, has a good chance of improving vision. Treatment of the hemangioma, before or during vitrectomy, usually results in tumor regression.

Subclinical capillary changes in non-proliferative diabetic retinopathy.

Purpose. To establish adaptive optics scanning laser ophthalmoscopy as a method to detect and characterize microscopic signs of diabetic retinopathy in capillaries and cone photoreceptors in the parafovea. Methods. Recently, adaptive optics scanning laser ophthalmoscope (AOSLO) has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intraretinal microvascular abnormalities, and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. Results. Capillaries and cone photoreceptors were visualized using the AOSLO without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance as well as the formation of tiny capillary bends similar in appearance to intraretinal microvascular abnormalities. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared with normal data but stable across all visits. Conclusions. AOSLO imaging can be used to longitudinally track capillaries, leukocytes, and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries as well as formation and disappearance of microaneurysms.

Central Serous Chonoretinopathy Occurring in Patients 60 Years of Age and Older

The authors report on 13 eyes in 13 patients, 60 years of age or older, with idiopathic central serous chorioretinopathy, a condition that typically presents in adults between the ages of 30 and 50 years. In older patients, this condition can easily be mistaken for macular degeneration with subretinal neovascularization. None of the patients in this series had soft drusen, geographic atrophy, or subretinal neovascularization, signs of age-related macular degeneration or other retinal or macular disease. Subretinal nea vascularization was not seen either at the time of initial diagnosis or during follow-up. The clinical, biomicroscopic, and fluorescein angiographic characteristics of this entity are described. The clinical course of 7 of these 13 eyes that underwent laser photocoagulation treatment is also described.