The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18.

OBJECTIVES: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

One-year outcomes of panretinal photocoagulation in proliferative diabetic retinopathy.

PURPOSE: To describe the clinical features and complications of diabetic retinopathy, visual acuity, and number of repeat treatments after panretinal photocoagulation for proliferative diabetic retinopathy in a tertiary care center. METHODS: A cohort study was conducted with data collection from medical records of patients undergoing panretinal photocoagulation between 1985 and 1995 at the Scheie Eye Institute; 297 eyes of 186 patients were eligible for study. RESULTS: The presence of neovascularization of the disk at baseline, an earlier onset of diabetes, and a shorter duration of disease before panretinal photocoagulation were the strongest risk factors for needing an additional panretinal photocoagulation treatment. Sixty-two percent of eyes with poor visual acuity (< or =20/200) at baseline still had poor visual acuity at 1 year, and 76% with good visual acuity (> or =20/40) at baseline maintained good visual acuity at 1 year. Poor vision at baseline was the only risk factor for having poor vision at 1 year. Vitreous hemorrhage was present in 44% of eyes at baseline. New vitreous hemorrhage developed in 37% of eyes during the first year after panretinal photocoagulation. A traction retinal detachment was present in 4% of eyes at baseline and newly developed in 6% of eyes during follow-up. A repeat panretinal photocoagulation treatment was performed in 39% of eyes after initial treatment. A vitrectomy was performed in 10% of eyes from baseline through the 1-year follow-up visit. CONCLUSIONS: The data from this study are useful for counseling patients with respect to likely visual outcome, possibility of major complications from proliferative diabetic retinopathy, and the chance of undergoing additional laser treatment after panretinal photocoagulation.

Psychophysical evidence for rod vulnerability in age-related macular degeneration.

PURPOSE: To determine whether there is rod system dysfunction in the central retina of patients with age-related macular degeneration (AMD). METHODS: Dark-adapted sensitivity (500-nm stimulus) and light-adapted sensitivity (600 nm) were measured psychophysically at 52 loci in the central 38 degrees (diameter) of retina in 80 patients with AMD, and results were compared with those from older adult normal controls. All dark-adapted data were corrected for preretinal absorption. RESULTS: Mean field dark-adapted sensitivity was significantly lower in AMD patients as a group than in normal subjects. Within the AMD group were subsets of patients with normal mean dark- and light-adapted sensitivities; reduced dark-adapted sensitivities without detectable light-adapted losses; both types of losses; and, least commonly, only light-adapted losses. Regional retinal analyses of the dark-adapted deficit indicated the greatest severity was 2 degrees to 4 degrees or approximately 1 mm from the fovea, and the deficit decreased with increasing eccentricity. CONCLUSIONS: These psychophysical results are consistent with histopathologic findings of a selective vulnerability for parafoveal rod photoreceptors in AMD. The different patterns of rod and cone system losses among patients at similar clinical stages reinforces the notion that AMD is a group of disorders with underlying heterogeneity of mechanism of visual loss. Dark-adapted macula-wide testing may be a useful complement to the more traditional outcome measures of fundus pathology and foveal cone-based psychophysics in future AMD trials.

Laser-induced drusen reduction improves visual function at 1 year. Choroidal Neovascularization Prevention Trial Research Group.

OBJECTIVE: To describe the relationship of laser-induced drusen reduction to change in visual function at 1 year among patients enrolled in the Choroidal Neovascularization Prevention Trial (CNVPT). DESIGN: Comparison of groups with and without drusen reduction; follow-up of a randomized controlled trial. PARTICIPANTS: Evaluations of drusen and visual acuity at baseline and at 1 year were performed for 351 eyes of the 432 eyes enrolled in the CNVPT Bilateral Drusen Study and Fellow Eye Study (81%). One hundred eighty-four eyes were assigned to observation, and 167 eyes were assigned to laser treatment. Eyes with conditions that precluded an analysis of drusen reduction, such as those that developed choroidal neovascularization (CNV) within the first year, are excluded from this analysis. METHODS: Change in macular drusen between initial visit and after 1 year was assessed by side-by-side grading by evaluators masked to information on visual function. Visual acuity, contrast threshold, and critical print size were measured by certified visual function examiners. MAIN OUTCOME MEASURES: Change in visual acuity is the primary outcome. Change in contrast threshold and change in critical print size are secondary outcome measures. RESULTS: Laser-treated eyes with 50% or more drusen reduction at 1 year had more 1- and 2-line increases in visual acuity and less losses in visual acuity compared with laser-treated eyes with less drusen reduction or with observed eyes (P = 0.001). Similar improvements were noted for contrast threshold but not critical print size at 1 year. CONCLUSIONS: Laser-induced drusen reduction is associated with improved visual acuity and contrast sensitivity in eyes at 1 year. Longer term effects of laser-induced drusen reduction on visual function require additional observation. The overall potential value of laser treatment in eyes with high-risk drusen requires consideration of not only short-term effects on vision but also the effects of CNV and atrophy on vision.

The sensory world of the platypus.

Vision, audition and somatic sensation in the platypus are reviewed. Recent work on the eye and retinal ganglion cell layer of the platypus is presented that provides an estimate of visual acuity and suggests that platypus ancestors may have used vision, as well as the bill organ, for underwater predation. The combined electroreceptor and mechanoreceptor array in the bill is considered in detail, with special reference to the elaborate cortical structure, where inputs from these two sensory arrays are integrated in a manner that is astonishingly similar to the stripe-like ocular dominance array in primate visual of cortex, that integrates input from the two eyes. A new hypothesis, along with supporting data, is presented for this combined mechanoreceptive-electroreceptive complex in platypus cortex. Bill mechanoreceptors are shown to be capable of detecting mechanical waves travelling through the water from moving prey. These mechanical waves arrive after the electrical activity from the same prey, as a function of distance. Bimodal cortical neurones, sensitive to combined mechanical and electrical stimulation, with a delay, can thus signal directly the absolute distance of the prey. Combined with the directional information provided by signal processing of the thousands of receptors on the bill surface, the stripe-like cortical array enables the platypus to use two different sensory systems in its bill to achieve a complete, three-dimensional 'fix' on its underwater prey.

A model of the incidence and consequences of choroidal neovascularization secondary to age-related macular degeneration. Comparative effects of current treatment and potential prophylaxis on visual outcomes in high-risk patients.

OBJECTIVE: To describe the comparative impact of current and preventive treatments on incidence of choroidal neovascularization (CNV) and severe vision loss in patients with bilateral soft drusen (BSD). DESIGN: Stochastic model. SETTING: US population. PATIENTS: Prevalence cohort of white patients 43 years or older with BSD. INTERVENTIONS: Application of prophylaxis of 10% to 50% efficacy to 1 or both eyes of patients with BSD, application of laser photocoagulation to eligible CNV lesions, or both. MAIN OUTCOME MEASURES: Proportion of patients with BSD after 10 years with unilateral and bilateral CNV and resultant unilateral and bilateral vision loss to visual acuity of 20/200 or worse. RESULTS: The natural history of patients with BSD generated by the model shows that 12.40% of these patients develop either unilateral or bilateral CNV within 10 years of their entry into the BSD prevalence cohort. Bilateral disease occurs in 3.86% of patients with BSD within 10 years. The proportion of patients with BSD becoming legally blind from CNV within 10 years is 2.54% if no treatment is performed. Current laser treatment for CNV decreases the proportion with legal blindness within 10 years to 2.24%. The addition of a preventive treatment of 10% efficacy applied bilaterally to the current laser treatment regimen decreases the proportion with legal blindness to 1.86%; a 25% effective preventive treatment decreases it to 1.34%. Comparatively, preventive treatment of 10% and 25% efficacy given to the fellow eye only after the first eye has developed CNV decreases the proportion of legally blind patients at 10 years only to 2.06% and 1.77%, respectively. All outcomes vary with sex and age at entry into the BSD cohort. CONCLUSIONS: Patients with BSD face a 12.40% risk of developing CNV within 10 years. The addition of even a modest (10% effective) bilateral preventive treatment to the current regimen for CNV would more than double the prevention of legal blindness in the BSD population relative to current laser treatment; a preventive treatment of 33% efficacy more than halves the rate of legal blindness caused by CNV. Preventive treatment given to the fellow eye only after the first develops CNV has substantially less impact.

Macular hole.

A macular hole is a full-thickness defect of retinal tissue involving the anatomic fovea, thereby affecting central visual acuity. Macular holes have been associated with myriad ocular conditions and originally were described in the setting of trauma. The pathogenesis of idiopathic, age-related macular holes remains unclear despite a litany of theories. Recently, Gass has described an updated biomicroscopic classification of macular holes and postulated that tangential vitreous traction may play a role. Cellular components surrounding the rim of macular holes may also contribute tangential traction forces and elevate the rim. Pseudomacular holes may be mistaken for macular hole lesions, despite careful clinical examination. Careful biomicroscopic examination with a contact lens and use of the Watzke and laser aiming beam tests help to ensure accurate diagnosis. Newer imaging technology, such as optical coherence tomography, helps distinguish true macular holes from pseudoholes and may provide additional insight into the pathogenesis of this condition. Surgical management with or without pharmacosurgical adjuncts can improve vision in select cases. The most common surgical complication is progressive lens opacification in phakic patients.

Foveolar choroidal blood flow in age-related macular degeneration.

PURPOSE: To compare measurements of the foveolar choroidal blood circulation in subjects with nonexudative, age-related macular degeneration (AMD) with those of control subjects. METHODS: Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the center of the fovea. Measurements were obtained in 20 eyes of 20 subjects with 10 or more large drusen, visual acuity of 20/32 or better, and no evidence of choroidal neovascularization. Findings obtained in these subjects were compared with those of 10 eyes of 10 age- and blood pressure-matched control subjects with no large drusen. Foveolar choroidal blood flow measurements were obtained by asking the study participants to fixate on a probing laser beam. RESULTS: No significant differences in average age, blood pressure, or intraocular pressure were observed between subjects with AMD and control subjects. In subjects with AMD, average ChBVol was 0.24 +/- 0.08 (+/- 1 SD) arbitrary units (AU); this value was 33% lower than that of control subjects (0.36 +/- 0.11 AU; two-tailed, independent Student's t-test, P = 0.005). Average ChBVel, conversely, was not significantly different from normal (0.44 +/- 0.07 AU) in subjects with AMD (0.44 +/- 0.10 AU). Average ChBFlow in subjects with AMD (8.7 +/- 3.1 AU) was 37% lower than that of control subjects (13.7 +/- 3.5 AU) (P = 0.0005). Average blood flow pulsatility was 6% higher in subjects with AMD (0.71 +/- 0.15) than in control subjects (0.66 +/- 0.14), but this difference was not statistically significant (P = 0.42). CONCLUSIONS: Average ChBFlow in the nonexudative stages of AMD is lower than that of age-matched controls, and the effect is caused mainly by a decrease in ChBVol. Further studies are needed to elucidate whether decreased ChBFlow plays a role in the development of choroidal neovascularization, and whether ChBFlow measurements may help identify subjects with AMD at risk for developing choroidal neovascularization.

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.