Judith Alexander

Translocation of the Retina for Management of Subfoveal Choroidal Neovascularization II: A Preliminary Report in Humans

Abstract Purpose: To report a surgical method for translocation of the foveal retina in eyes with subfoveal choroidal neovascularization. Methods: In three eyes of three patients, a crescent-shaped, partial-thickness scleral resection was performed near the equator at either the superotemporal or the inferotemporal quadrant. A near-total retinal detachment was created; then the edges of the resected sclera were sutured, causing shortening of the sclera with subsequent reattachment of the retina, resulting in translocation of the fovea to an area overlying nonfoveal retinal pigment epithelium and choroid. Results: In three eyes of three patients, the fovea was surgically translocated to overlie retinal pigment epithelium that preoperatively was not underlying the fovea. In two patients, laser photocoagulation was applied to the choroidal neovascularization that, after translocation of the fovea, was no longer subfoveal, so that the photocoagulation was not associated with immediate visual loss. After a follow-up of 4 to 6 months, the visual acuity had improved in all patients (from 20/126 preoperatively to 20/70 in one patient, from 20/200 preoperatively to 20/70 in the second, and from 20/160 to 20/30 in the third). The patients noted distortion or tilting of the images, which improved over time. Conclusions: Limited foveal translocation may offer a therapeutic modality to preserve or improve vision in cases of subfoveal choroidal neovascularization. Additional follow-up is needed to assess the impact of potential complications associated with the surgical procedure, such as retinal detachment, proliferative vitreoretinopathy, and cataract, as well as the possibility of recurrent choroidal neovascularization.

Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial.

OBJECTIVE To report the 2-year incidence of raised intraocular pressure (IOP) and glaucomatous optic nerve damage in patients with uveitis randomized to either fluocinolone acetonide (FA) implants or systemic therapy. Secondarily, we sought to explore patient and eye characteristics associated with IOP elevation or nerve damage. DESIGN A randomized, partially masked trial in which patients were randomized to either FA implants or systemic therapy. PARTICIPANTS Patients aged ≥ 13 years with noninfectious intermediate, posterior, or panuveitis active within the prior 60 days for which systemic corticosteroids were indicated were eligible. METHODS Visual fields were obtained at baseline and every 12 months using the Humphrey 24-2 Swedish interactive threshold algorithm (SITA) fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3-, 6-, 12-, and 24-month follow-up visits. Masked examiners measured IOP at every study visit. MAIN OUTCOME MEASURES Glaucoma was diagnosed based on an increase in optic nerve cup-to-disc ratio with visual field worsening or increased cup-to-disc ratio alone, for cases where visual field change was not evaluable, because of missing data or severe visual field loss at baseline. RESULTS Most patients were treated as assigned; among those evaluated for glaucoma, 97% and 10% of patients assigned to implant and systemic treatment, respectively, received implants. More patients (65%) assigned to implants experienced an IOP elevation of ≥ 10 mmHg versus 24% assigned to systemic treatment (P<0.001). Similarly, 69% of patients assigned to the implant required IOP-lowering therapy versus 26% in the systemic group (P<0.001). Glaucomatous optic nerve damage developed in 23% versus 6% (P<0.001) of implant and systemic patients, respectively. In addition to treatment assignment, black race, use of IOP-lowering medications, and uveitis activity at baseline were associated with incident glaucoma (P<0.05). CONCLUSIONS Implant-assigned eyes had about a 4-fold risk of developing IOP elevation of ≥ 10 mmHg and incident glaucomatous optic neuropathy over the first 2 years compared with those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) is needed to avoid glaucoma when vision-threatening inflammation requires implant therapy. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Photographic Assessment of Baseline Fundus Morphologic Features in the Comparison of Age-related Macular Degeneration Treatments Trials

OBJECTIVE To describe the methods used for assessment of baseline fundus characteristics from color photography and fluorescein angiography (FA) in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to describe the relationship between these characteristics and visual acuity. DESIGN Randomized, masked, multicenter trial. PARTICIPANTS This investigation included 1185 participants of the CATT study. METHODS Baseline stereoscopic color fundus photographs and FAs of participants in the CATT study were assessed at a central fundus photograph reading center by masked readers. Replicate assessments of random samples of photographs were performed to assess intragrader and intergrader agreements. The association of the lesion characteristics with baseline visual acuity was assessed using analyses of variance and correlation coefficients. MAIN OUTCOME MEASURES Intragrader and intergrader reproducibility, visual acuity, and lesion characteristics. RESULTS Intragrader and intergrader reproducibility showed agreements ranging from 75% to 100% and weighted κ values ranging from 0.48 to 1.0 for qualitative determinations. The intraclass correlation coefficients were 0.96 to 0.97 for quantitative measurements of choroidal neovascularization (CNV) area and total area of CNV lesion. The mean visual acuity varied by the type of pathologic features in the foveal center: 64.5 letters (standard error, 0.7 letters) for fluid only, 59.0 letters (standard error, 0.5 letters) for CNV, and 58.7 letters (standard error, 1.3 letters) for hemorrhage (P<0.001). Fibrotic or atrophic scar present in the lesion, but not under the center of the fovea, also was associated with a markedly reduced visual acuity of 48.4 letters (standard error, 2.2 letters; P<0.0001). Although total area of CNV lesion was correlated weakly with visual acuity when all participants were assessed (Spearman correlation coefficient, ρ = -0.16; P<0.001), the correlation was stronger within patients with predominantly classic lesions (ρ = -0.42; P<0.001). CONCLUSIONS These results show that the methodology used for grading CATT fundus images has good reproducibility. As expected, larger total CNV lesion area and pathologic findings such as hemorrhage, fibrosis, and atrophy at baseline are associated with decreased visual acuity.

Prevalence of Ocular Fundus Pathology in Patients with Chronic Kidney Disease

BACKGROUND AND OBJECTIVES The objective of this study was to describe the prevalence of ocular fundus pathology in the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter, longitudinal study of individuals with varying stages of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this cross-sectional study, 45 degree digital photos of the disc and macula in both eyes were obtained by nonophthalmologic personnel using a nonmydriatic Canon CR-DGI fundus camera in 1936 individuals who participated in the CRIC study. Photographs were assessed in a masked manner by graders and a retinal specialist at a central photograph reading center. The purpose of this review was to inform participants quickly of conditions that warranted a complete eye examination by an ophthalmologist. RESULTS Among the 1936 participants who were photographed, 1904 (98%) had assessable photographs in at least one eye. Eye pathologies that required a follow-up examination by an ophthalmologist were identified in 864 (45%) of these 1904 participants. These eye pathologies included, among others, retinopathy (diabetic and/or hypertensive), a finding that was observed in 482 (25%) of these 1904 participants. Three percent (65 participants) of the 1904 participants had serious eye conditions that required urgent follow-up and treatment. Lower estimated GFR and cardiovascular disease were associated with greater eye pathology. Estimated GFR <30 ml/min per 1.73 m(2) was associated with a three times higher risk for retinopathy. CONCLUSIONS We found a high prevalence of fundus pathology in participants with CKD. This finding supports recommendations for regular complete eye examinations in the CKD population.

Variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration.

Objectives To investigate the variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration. Methods Eight graders, who included two TAP-certified ophthalmologists, three other retinal specialists, two fellows in vitreoretinal diseases, and a senior fundus photograph grader, evaluated fluorescein angiograms of six patients treated according to the Treatment for ARMD With Verteporfin (TAP) protocol at a single center. Each patient’s baseline angiogram was evaluated to determine whether the CNV lesion was predominantly (≥50%) classic. For each follow-up angiogram, at 3, 6, 12, and 24 months, the grader was required to determine whether fluorescein leakage was present. Six months after the initial gradings, each reader was again presented with the baseline angiogram for each patient and once again asked to determine whether the CNV lesion was predominantly classic without knowledge of the previous grading. All gradings were performed without knowledge of the clinical course. Results In grading initial visit and follow-up visit angiograms, the overall concordance rates were 81% and 82%, respectively. Concordance rates were not statistically different between the group as a whole when compared with the gradings of the two TAP-certified ophthalmologists. When initial visit angiograms were regraded, an intraobserver variability of 17% was noted. Overall, gradings were discordant with the majority opinion in approximately 19% of decisions. Conclusions Considerable variability can be expected in fluorescein angiography interpretation as the results of the TAP investigation are applied to clinical practice.

Association Between Retinopathy and Cardiovascular Disease in Patients With Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort [CRIC] Study)

Patients with chronic kidney disease experience co-morbid illnesses, including cardiovascular disease (CVD) and retinopathy. The purpose of the present study was to assess the association between retinopathy and self-reported CVD in a subgroup of the participants in the Chronic Renal Insufficiency Cohort study. For this observational, ancillary investigation, 2,605 Chronic Renal Insufficiency Cohort participants were invited to participate in the present study, and nonmydriatic fundus photographs in both eyes were obtained for 1,936 subjects. The photographs were reviewed in a masked fashion at a central photograph reading center. The presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed using standard protocols by trained graders who were masked to the information about the study participants. A history of self-reported CVD was obtained using a medical history questionnaire. Kidney function measurements and traditional and nontraditional risk factors for CVD were obtained from the Chronic Renal Insufficiency Cohort study. A greater severity of retinopathy was associated with a greater prevalence of any CVD, and this association persisted after adjustment for the traditional risk factors for CVD. The presence of vascular abnormalities usually associated with hypertension was also associated with increased prevalence of CVD. We found a direct relation between CVD prevalence and mean venular caliber. In conclusion, the presence of retinopathy was associated with CVD, suggesting that retinovascular pathology might indicate macrovascular disease, even after adjustment for renal dysfunction and traditional CVD risk factors. This would make the assessment of retinal morphology a valuable tool in CKD studies of CVD outcomes.

Description of the Age-Related Eye Disease Study 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial.

OBJECTIVE To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). METHODS Eligibility criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. RESULTS Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. CONCLUSIONS The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.

Characteristics of Choroidal Neovascularization in the Complications of Age-Related Macular Degeneration Prevention Trial

OBJECTIVE To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). DESIGN Cross-sectional descriptive study within a multicenter, randomized clinical trial. PARTICIPANTS Patients who developed CNV during CAPT follow-up. METHODS Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. MAIN OUTCOME MEASURES Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. RESULTS Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were <or=2 MPS disc areas. Visual acuity was >or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. CONCLUSIONS When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

Relation between retinal thickening and clinically visible fundus pathologies in mild nonproliferative diabetic retinopathy

BACKGROUND AND OBJECTIVE To determine the association of retinal thickening (RT) with clinically observable retinal pathologies in eyes with mild nonproliferative diabetic retinopathy. PATIENTS AND METHODS Using an objective quantitative imaging method (Retinal Thickness Analyzer), the ratio relative to normal RT (RTI) was measured in 23 eyes with and 35 eyes without clinically observable diabetic fundus pathology. RTI was analyzed in relation to presence of mild diabetic retinal lesions in the +/-0.5 mm vicinity. RESULTS The percent of eyes with RTI significantly above normal values did not differ significantly between eyes with and without retinopathy (30% vs 34%). Mean RTI was not associated with local presence of microaneurysms (P=0.92), soft exudates (P=0.55), or retinal hemorrhages (P=0.31). Areas without hard exudates had significantly greater mean RTI (1.10) than areas with exudates (0.97, P=0.009). CONCLUSION In diabetic patients with mild retinopathy, areas with and without clinically observable retinal pathologies had similar retinal thickness. We conclude that clinical strategies for detection of retinal thickening should not be limited to areas with visible fundus pathologies.

Utility of Digital Stereo Images for Optic Disc Evaluation

PURPOSE To assess the suitability of digital stereo images for optic disc evaluations in glaucoma. METHODS Stereo color optic disc images in both digital and 35-mm slide film formats were acquired contemporaneously from 29 subjects with various cup-to-disc ratios (range, 0.26-0.76; median, 0.475). Using a grading scale designed to assess image quality, the ease of visualizing optic disc features important for glaucoma diagnosis, and the comparative diameters of the optic disc cup, experienced observers separately compared the primary digital stereo images to each subjects 35-mm slides, to scanned images of the same 35-mm slides, and to grayscale conversions of the digital images. Statistical analysis accounted for multiple gradings and comparisons and also assessed image formats under monoscopic viewing. RESULTS Overall, the quality of primary digital color images was judged superior to that of 35-mm slides (P < 0.001), including improved stereo (P < 0.001), but the primary digital color images were mostly equivalent to the scanned digitized images of the same slides. Color seemingly added little to grayscale optic disc images, except that peripapillary atrophy was best seen in color (P < 0.0001); both the nerve fiber layer (P < 0.0001) and the paths of blood vessels on the optic disc (P < 0.0001) were best seen in grayscale. The preference for digital over film images was maintained under monoscopic viewing conditions. CONCLUSIONS Digital stereo optic disc images are useful for evaluating the optic disc in glaucoma and allow the application of advanced image processing applications. Grayscale images, by providing luminance distinct from color, may be informative for assessing certain features.