Observational study of subclinical diabetic macular edema.

PURPOSE: To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. METHODS: In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 µm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 µm from baseline and a CPT of at least 300 µm, or treatment for DME (performed at the discretion of the investigator). RESULTS: The cumulative probability of meeting an increase in OCT CPT of at least 50 µm from baseline and a CPT of at least 300 µm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. CONCLUSIONS: Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification.

Retinal angiomatous proliferation or retinal anastomosis to the lesion.

Much debate exists within the literature with respect to the variant of neovascular age-related macular degeneration (AMD) known as retinal angiomatous proliferation (RAP). We prefer the term retinal anastomosis to the lesion (RAL), as we believe that the choroidal neovascularization (CNV) lesion precedes the development of an anastomosing retinal vessel to this lesion. Natural history data surrounding RAP lesions are available through analysis of the eyes with subfoveal occult CNV within the placebo arm of the Verteporfin in Photodynamic Therapy (VIP) trial. Although many reports ascribe a poor prognosis to RAP lesions, the data suggest that the true natural history of RAP lesion may be highly variable and similar to that of other CNV lesions. Information from clinical trials suggests that the response of RAP lesions to CNV treatments may also be similar to that of other variants of neovascular AMD.

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with diabetic retinopathy.

PURPOSE: To report the use of photodynamic therapy (PDT) with verteporfin in three patients with choroidal neovascularization (CNV) from age-related macular degeneration and underlying diabetic retinopathy. The level of diabetic retinopathy would have excluded these patients from participation in previously reported randomized clinical trials evaluating PDT with verteporfin due to a theoretic concern of damage to the overlying retinal vasculature. DESIGN: Retrospective interventional case series. METHODS: Three patients from a referral practice with at least severe nonproliferative diabetic retinopathy and a history of clinically significant macular edema developed loss of vision from concurrent choroidal neovascularization evaluated with fundus photography and fluorescein angiography before and after PDT with verteporfin to identify adverse retinal vascular events. RESULTS: Four eyes in three patients had PDT using verteporfin. Three eyes received two treatments. With short follow-up, visual acuity remained stable in two eyes, improved from 20/400 to 20/320 in one eye, and decreased from 20/200 to 20/400 in one eye. Fluorescein angiograms at intervals from 2 weeks to 3 months after PDT showed no damage to the retinal vasculature or progression of the diabetic retinopathy, but did show a decreased area of fluorescein leakage from CNV. One eye that had new subretinal hemorrhage following treatment appeared to show new vasculopathy on initial evaluation of the post-treatment angiogram. Retrospective review suggested that the subretinal hemorrhage provided increased contrast to more easily visualize vasculopathy that was present before the PDT. CONCLUSIONS: Three patients with diabetic retinopathy undergoing a total of seven PDT treatments with verteporfin in four eyes had no new retinal vascular abnormalities develop. No other atypical responses of CNV to PDT were noted except new subretinal hemorrhage, providing increased contrast of the overlying vasculature, which gave the false impression of the development of new vasculopathy in one eye. Patients with diabetic retinopathy who have concurrent CNV for which PDT with verteporfin is recommended should be cautioned regarding the theoretical concerns of harming the retinal vasculature. Periodic surveillance for such concerns seems warranted until more experience is obtained.

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.

Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study.

OBJECTIVE: To determine the causes of blindness and visual impairment in a population-based sample of older Americans. METHODS: A random sample of 3821 residents of Salisbury, Md, between the ages of 65 and 84 years was identified from Medicare records. Sixty-six percent (2520 persons) agreed to undergo an eye examination; 26% of the participants were African American. The clinical examination included acuity testing with an Early Treatment Diabetic Retinopathy Study chart and standardized refraction testing for those with a visual acuity worse than 20/30, slitlamp and dilated retinal examination by an ophthalmologist, tonometry, lens and fundus photography, and a suprathreshold visual field test. Visual impairment was defined as a best-corrected acuity in the better-seeing eye worse than 20/40 and better than 20/200, while blindness was acuity in the better-seeing eye of 20/200 or worse. For those with a visual acuity worse than 20/40 in either eye, one or more causes were assigned by an ophthalmologist and a final cause for each eye was confirmed by a panel of 3 subspecialty ophthalmologists (O.D.S., H.A.Q., and S.B.B.) based on all available evidence. RESULTS: Bilateral presenting acuity worse than 20/40 increased from 4% in the 65- to 74-year age group to 16% in the 80- to 84-year age group. One third of those with presenting acuity worse than 20/40 improved to 20/40 or better with refraction. Overall, 4.5% had a best-corrected acuity worse than 20/40. African Americans were more likely to remain visually impaired than were whites despite refraction (odds ratio [95% confidence interval], 1.7 [1.1-2.6]). Whites were most often impaired or blind from age-related macular degeneration (1.2% vs 0.5%; P=.09). African Americans had higher rates of impairment and blindness from cataract or posterior capsular opacification (2.7% vs 1.1%; P=.006), glaucoma (0.9% vs 0.1%; P=.006), and diabetic retinopathy (1.2% vs 0.2%; P=. 004). CONCLUSIONS: More than half of those with visual impairment or blindness had conditions that were either surgically treatable or potentially preventable. African Americans had a disproportionate number of blinding diseases, particularly those amenable to eye care intervention. Targeted interventions for specific populations to increase appropriate eye care use would greatly improve vision and function in older Americans. Arch Ophthalmol. 2000;118:819-825

Ketorolac treatment of pseudophakic cystoid macular edema identified more than 24 months after cataract extraction.

OBJECTIVE: To evaluate whether ketorolac ophthalmic drops prescribed four times a day can be associated with improved visual acuity and prompt resolution of edema for patients with pseudophakic cystoid macular edema identified more than 24 months after cataract surgery. DESIGN: Prospective, nonrandomized, comparative (subject self-controlled) trial. PARTICIPANTS: The records of nine patients who had pseudophakic cystoid macular edema more than 24 months after cataract surgery at the time treatment commenced were identified at the Wilmer Retinal Vascular Center from September 1, 1996, through March 1, 1997. MAIN OUTCOME MEASURES: Best-corrected visual acuities measured on a retroilluminated Bailey-Lovie chart approximately every 3 months, contact lens biomicroscopy, and fluorescein angiography following ketorolac. INTERVENTION: Commercially available ketorolac ophthalmic drops 0.5% were prescribed for the affected eye four times a day for at least 3 months and continued until edema resolved. RESULTS: Ten eyes of nine patients were identified more than 24 months after cataract extraction (median, 59 months). Seven eyes (70%) improved (mean, +3.2 lines; range, +1 to +13 lines), including six by 2 or more lines 3 months after treatment initiation. Two eyes (20%) were unchanged, and one eye (10%) was 1 line worse. All seven eyes that improved 1 line or more had some or complete angiographic resolution of fluorescein dye leakage. In these seven eyes, ketorolac was discontinued when dye leakage completely resolved or failed to continue to improve on periodic 3-month follow-up examinations. In all seven eyes, recurrence of edema was noted within 3 months after ketorolac was stopped. CONCLUSIONS: Chronic pseudophakic cystoid macular edema identified more than 24 months after cataract surgery can improve with topical ketorolac but probably requires persistent use.

Availability of color fundus photographs from previous visit affects practice patterns for patients with diabetes mellitus.

OBJECTIVE: To determine whether access to color fundus photographs from a patient's previous visit would alter the recommendations rendered to a cohort with diabetic retinopathy. PATIENTS AND METHODS: One hundred sixty patients with diabetic retinopathy returning for a follow-up visit and who had color fundus photographs obtained at a previous visit were evaluated by trained retina specialists. Their clinical impression and recommendations regarding management of diabetic retinopathy were recorded without reference to previous photographs. Color fundus photographs from the patient's most recent visit were then reviewed and new recommendations with regard to appropriate treatment and follow-up were recorded. RESULTS: In 21% of cases, after reviewing the patient's most recent color fundus photographs, the clinical recommendation changed. In 14% of cases, photographs clearly demonstrated that the patient's condition was stable or improved, resulting in a change from recommending treatment to recommending deferral of treatment. In 4% of cases, photographs clearly demonstrated clinical worsening and the recommendation was changed from observation to treatment. In 3% of cases, review of photographs prompted a change in the recommended follow-up interval. CONCLUSION: Access to color fundus photographs from a patient's previous visit frequently changed the clinical recommendations made to patients with diabetic retinopathy regarding appropriate treatment and follow-up. Availability of color fundus photographs therefore has implications about quality of care and may affect the cost of care.

Age-related macular degeneration and risk factors for the development of choroidal neovascularization in the fellow eye.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world. Most of the severe vision loss associated with AMD is due to the development of choroidal neovascularization (CNV). The specific causes of AMD and in particular, its neovascular phase, remain uncertain. During the past two decades a number of large prospective clinical trials, observational epidemiologic studies, and population-based cohort studies have furthered our understanding of this blinding ocular condition. The Macular Photocoagulation Study has received praise for its many contributions in the laser treatment of neovascular complications of AMD; however, these trials have made other significant contributions by helping to better define the natural history of AMD, and in particular, risk factors for the development of CNV in eyes with non-neovascular disease. This type of information may provide significant clues for researchers regarding disease pathogenesis and identify a high-risk group in whom to target new treatment strategies. For patients currently diagnosed with macular degeneration, this information can lead to a better understanding of their condition and a more accurate prognosis of their ocular health and vision status. This article reviews information from a variety of sources to investigate incidence rates and risk factors for the development of CNV in the fellow eye of patients with AMD and unilateral neovascular maculopathy.

Occult choroidal neovascularization in age-related macular degeneration. A natural history study.

OBJECTIVE: To explore morphological and vision changes in untreated eyes with subfoveal choroidal neovascularization (CNV) that have poorly demarcated boundaries. DESIGN: Analysis of photographs of untreated patients with poorly demarcated occult CNV participating in a prospective clinical trial evaluating laser treatment compared with observation. SETTING: Two tertiary retinal referral centers. PATIENTS: Symptomatic individuals with poorly demarcated subfoveal occult CNV associated with age-related macular degeneration. MAIN OUTCOME MEASURES: Change in size of lesion, development of classic CNV, change in vision, and development of subretinal fibrosis. RESULTS: During follow-up (9-12 months), 32% of the occult choroidal neovascular lesions more than doubled their original size. Classic CNV developed in 52% of eyes that started without it. The median loss in visual acuity was 2.5 lines. Eyes with classic CNV or subretinal blood or both at baseline developed subretinal fibrosis more frequently and lost more visual acuity, but not to a statistically significant degree. CONCLUSIONS: The morphological changes of eyes with subfoveal occult CNV in which the boundaries are poorly demarcated in variable; the presence of subretinal blood or a component of classic CNV may influence the prognosis for further loss of vision.

Macular scatter ('grid') laser treatment of poorly demarcated subfoveal choroidal neovascularization in age-related macular degeneration. Results of a randomized pilot trial.

OBJECTIVES: To determine the effects of macular scatter ("grid") laser photocoagulation compared with observation on the visual function of eyes with subfoveal choroidal neovascularization (CNV) that has poorly demarcated boundaries and to provide preliminary data for the evaluation of the feasibility and design of a larger, definitive trial. DESIGN: Randomized pilot clinical trial. SETTING: Two tertiary care retinal referral practices. PATIENTS: Symptomatic individuals with subfoveal CNV secondary to age-related macular degeneration in whom fluorescein angiography showed occult CNV with poorly demarcated boundaries; classic CNV was allowed but did not need to be present for entry into the study. MAIN OUTCOME MEASURE: Change in visual acuity from baseline to specified time periods. RESULTS: Fifty-two eyes were assigned to observation. Fifty-one eyes were assigned randomly to treatment consisting of macular scatter ("grid") laser photocoagulation to the area of CNV. The treatment protocol for 8 of these eyes also included confluent laser photocoagulation to areas of classic CNV. The average visual acuity decrease from baseline was greater in the treated than in the observed group. The difference between these groups was greatest within the first year after study enrollment. At 24 months, slightly more than 40% of the eyes in each group had lost 6 or more lines of visual acuity. Similar results were noted for the subgroup of eyes initially with angiographic features of occult CNV but no classic CNV. CONCLUSIONS: These short-term study results suggest that macular scatter ("grid") laser treatment is not beneficial and is possibly harmful compared with observation for symptomatic subfoveal CNV with poorly demarcated boundaries in age-related macular degeneration. With or without treatment, a significant proportion of these patients are at risk of severe visual loss within 2 years of seeking treatment, even when the eye initially has occult CNV and no classic CNV.

Detection of diabetic macular edema: Nidek 3Dx stereophotography compared with fundus biomicroscopy.

PURPOSE: To assess the use of the Nidek 3Dx simultaneous stereophotography camera in diabetic patients, comparing the detection of clinically significant macular edema by fundus biomicroscopy to detection by the Nidek 3Dx simultaneous fundus stereophotograph. METHODS: Two hundred eight eyes of 123 diabetic patients at the Wilmer Retinal Vascular Center were examined for this prospective study between August 1993 and October 1993. Each patient was examined by one of three retina specialists by contact lens biomicroscopy for clinically significant macular edema and foveal center thickening. Nidek 3Dx fundus stereophotographs were obtained and graded independently for clinically significant macular edema and foveal center thickening by a fourth ophthalmologist masked from the clinical examination findings. Percent agreement, kappa statistic, and weighted kappa statistic were determined for the two diagnostic methods. RESULTS: One hundred eighty-four (88%) of the 208 stereophotographs were of sufficient quality to detect clinically significant macular edema; 175 (84%) of the 208 stereophotographs detected foveal center thickening. The agreement between the clinician and the photographic grading, measured by weighted kappa, was 0.52 for clinically significant macular edema and 0.58 for foveal center thickening, representing fair to good agreement beyond chance. Agreement was improved when normal fundus Nidek stereophotographs were available as standards for comparison. CONCLUSIONS: The Nidek 3Dx camera is suitable for photographic detection of clinically significant macular edema and may have a potential advantage over conventional cameras by achieving good-quality, gradable stereophotographs in a large proportion of photographed eyes.

Are antioxidants or other supplements protective for age-related macular degeneration?

As the number of individuals with age-related macular degeneration increases, the economic and social consequences of this blinding disease rise. No proven preventive measures exist to halt development or progression of this disease. The specific insults that trigger and perpetuate age-related macular degeneration are unknown; however, it may be the result of repetitive oxidative injuries. Several studies suggest a possible protective role for antioxidant micronutrients and other trace minerals, but data for specific antioxidants have been inconsistent between studies. Although promising, the preliminary evidence is limited. Reliable data on whether antioxidant vitamins or trace minerals decrease the development or progression of age-related macular degeneration will emerge from several ongoing large-scale randomized clinical trials. Based on the currently available information, it is not possible to recommend antioxidant micronutrient supplementation to protect against development or retard progression of age-related macular degeneration.

Angiographic features and outcome of questionable recurrent choroidal neovascularization.

PURPOSE: We sought to identify specific fluorescein angiographic patterns that may have led to the diagnosis of questionable recurrent choroidal neovascularization. We evaluated follow-up information to determine whether any specific angiographic patterns could be used to identify patients at high risk for definite recurrence. METHODS: We identified fluorescein angiograms graded as questionable for recurrent choroidal neovascularization that were taken from a previous prospective study involving 401 consecutive follow-up visits of patients treated with photocoagulation for choroidal neovascularization. We reviewed these angiograms to identify specific angiographic patterns that might have led to the classification of questionable recurrent choroidal neovascularization. Angiograms from visits subsequent to a questionable recurrence were reviewed to determine which patterns, if any, were associated with an increased risk for a definite recurrence to develop later. RESULTS: Forty-four eyes (44 patients) with questionable recurrences (of which 40 had at least four months of follow-up) were categorized into six angiographic patterns. The three most common patterns included the following: (1) focal staining along the edge of the laser lesion (20 cases, 15 subsequently recurred); (2) blocked fluorescence from subretinal hemorrhage not documented at the previous visit (eight cases, five subsequently recurred); (3) speckled hyperfluorescence noted beyond the edge of the laser lesion (eight cases, six subsequently recurred). CONCLUSIONS: Questionable recurrent choroidal neovascularization may be identified by specific angiographic patterns. Focal staining along the edge of the laser lesion and speckled hyperfluorescence were the patterns that were most likely to progress to definite recurrence.

Preventative ophthalmology. Age-related macular degeneration.

PURPOSE: This report was designed to review the current knowledge about preventing the development or progression of age-related macular degeneration (AMD) and visual loss associated with this entity in practical terms for the comprehensive ophthalmologist. METHODS: Animal studies, epidemiologic studies, and clinical trials identified through the use of MEDLINE, a reference list of articles reviewed, and personal contact with experts in this area provided information reviewed for this report. RESULTS: Reports concerning ultraviolet and visible light provide limited, inconsistent, and conflicting data to support the theory that light exposure leads to AMD. Micronutrient supplementation is a provocative but largely unproven hypothesis. Positive associations of cigarette smoking and cardiovascular disease or certain risk factors for cardiovascular disease with AMD provide potential clues as to the underlying pathogenesis of AMD and are yet another reason to treat these health problems. Drusen may disappear after laser to the macula; however, this intervention will require careful, randomized, prospective trials to determine if this therapy can reduce the risk of choroidal neovascularization and visual loss developing in patients with AMD. CONCLUSIONS: It is reasonable to have individuals wear sunglasses for comfort and possible protection from ultraviolet light exposure to all ocular structures (especially the lens) at little or no risk to the patient. Physicians probably should be reluctant to prescribe micronutrients or suggest other interventions (such as laser to drusen) until their health claims have been substantiated and their long-term safety soundly established.

An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.