W. R. Freeman

Comparison of laser ray-tracing and skiascopic ocular wavefront-sensing devices.

PurposeTo compare two wavefront-sensing devices based on different principles.MethodsThirty-eight healthy eyes of 19 patients were measured five times in the reproducibility study. Twenty eyes of 10 patients were measured in the comparison study. The Tracey Visual Function Analyzer (VFA), based on the ray-tracing principle and the Nidek optical pathway difference (OPD)-Scan, based on the dynamic skiascopy principle were compared. Standard deviation (SD) of root mean square (RMS) errors was compared to verify the reproducibility. We evaluated RMS errors, Zernike terms and conventional refractive indexes (Sph, Cyl, Ax, and spherical equivalent).ResultsIn RMS errors reading, both devices showed similar ratios of SD to the mean measurement value (VFA: 57.5±11.7%, OPD-Scan: 53.9±10.9%). Comparison on the same eye showed that almost all terms were significantly greater using the VFA than using the OPD-Scan. However, certain high spatial frequency aberrations (tetrafoil, pentafoil, and hexafoil) were consistently measured near zero with the OPD-Scan.ConclusionBoth devices showed similar level of reproducibility; however, there was considerable difference in the wavefront reading between machines when measuring the same eye. Differences in the number of sample points, centration, and measurement algorithms between the two instruments may explain our results.

Choroidal melanoma microcirculation with confocal indocyanine green angiography before and 1 year after radiation brachytherapy.

Purpose: The authors previously demonstrated that confocal indocyanine green (ICG) angiography is capable of imaging the microcirculation of choroidal melanomas. The purpose of this study is to report their observations regarding the response of the microcirculation using confocal ICG at 1 year after radiation brachytherapy. Methods: Thirteen patients with unilateral choroidal melanoma were examined once before and several times up to 1 year after radiation brachytherapy (Iodine‐125 or Ruthenium‐106 plaque). At each visit, a complete ophthalmologic examination including standardized echography and fluorescein and ICG angiography was obtained, the latter using a confocal scanning laser ophthalmoscope. Results: In 10 patients (77%), the tumor microcirculation changed considerably within 1 year after treatment. Distortion, thickening, thinning, and complete obliteration of vessels could be observed. In the other 3 patients (23%), no changes in the microcirculation were noticed within the observation period. Conclusions: Follow‐up with confocal ICG of choroidal melanomas after treatment with local radiation brachytherapy allows for visualization of the microcirculation reaction following radiation brachytherapy. This provides the clinician with additional information for the posttreatment monitoring of these patients. Confocal ICG might also be a useful tool to monitor the effects of future antiangiogenesis‐based tumor therapies in choroidal melanomas.

Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

PurposeTo evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA).MethodsOverall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined.ResultsBCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test–retest ranged from 0.100 to 0.139 logMAR.ConclusionThe CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.

THE AGAR SANDWICH TECHNIQUE FOR RETINAL BIOPSY PROCESSING

Background The authors developed an agar sandwich technique for retinal biopsy processing. This tissue agar embedding technique allows for a rapid and reliable method to handle and transport retinal biopsies from the operative field to the histology laboratory. Methods Biopsies from rabbit retinas infected with herpes simplex virus, epiretinal membranes from patients with macular pucker, and retinas from patients with acute retinal necrosis were studied. Each retinal biopsy was fixed, mounted on an agar disc, and covered with liquid agar. Light microscopy, electron microscopy, immunocytochemistry, and polymerase chain reaction were employed on the agar-embedded tissue. Results The tissues remained mounted in the agar sandwich and maintained their orientation throughout the processing. The morphologic integrity, histologic characteristics, antigenic properties, and DNA quality all were preserved using the agar sandwich technique. Conclusion The agar sandwich technique is an efficient and simple technique for handling small biopsy specimens that require various analyses.

Toxicity of Subretinal Ribozyme to the Proliferating Cell Nuclear Antigen and 5-Fluorouracil in Rat Eyes

Purpose: To investigate the subretinal toxicity profile of the ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU), as well as the highest nontoxic subretinal dose of the mixture of the two agents in rat eyes. Methods: Brown-Norway rats received subretinal injections of 1 μ g, 10 μ g, and 100 μ g/μ l PCNA-Rz and 0.06 μ g/μ l, 0.3 μ g/μ l, and 1.5 μ g/μ l 5-FU in the right eyes, and the left eyes were injected with H-BSS as control. Each dose was tested on 5 eyes in a 5 μ l volume. In a second study, a combination of 5-FU (1.5 μ g/μ L) with varying 10–30–50 μ g/μ l doses of PCNA-Rz was tested in a regimen of four sequential subretinal injections. Toxicity was monitored by biomicroscopy, indirect ophthalmoscopy, electroretinography (ERG), and histology. Results: The highest nontoxic dose for subretinal PCNA-Rz was 10 μ g/μ l, whereas 100 μ g/μ l showed disturbance of pigmentation with corresponding histological changes of retinal photoreceptor loss and retinal pigment epithelium proliferation or irregularities. Subretinal injection of all three doses of 5-FU did not show any toxicity. Serial injections of a mixture of 1.5 μ g/μ l 5-FU with 10 μ g/μ l of PCNA-Rz was found to be safe in rat eyes. Conclusions: Subretinal injections of the combination of PCNA-Rz (10 μ g/μ l) and 5-FU (1.5 μ g/μ l) demonstrated to be safe in rat eyes during the course of this study, even with a multiple administration of four injections.

Zusammenhang von ICG-angiographisch nachgewiesenen “Networks” uvealer Melanome und Tumorrückbildungsgeschwindigkeit nach Brachytherapie

ZusammenfassungHintergrund. Die Tumorrückbildungsgeschwindigkeit nach Brachytherapie uvealer Melanome ist ein prognostisch signifikanter Faktor für die Entwicklung von Metastasen. Einen weiteren prognostisch ungünstigen Faktor für eine Metastasierung stellt der histologische Nachweis von “Networks” (Gefäßnetze) dar, die sich auch in der ICG-Angiographie darstellen lassen. Ziel ist die Untersuchung eines Zusammenhangs zwischen ICG-angiographisch nachweisbaren “Networks” und der Tumorrückbildungsgeschwindigkeit 1 Jahr nach Brachytherapie. Methoden. Bei 20 Patienten wurde die Tumorrückbildung der maximalen apikalen Tumorhöhe (MAH) innerhalb des 1. Jahres nach Brachytherapie ermittelt und mit dem präoperativen ICG-angiographischen Vorliegen von “Networks” verglichen. Zehn Patienten wurden mit Ru-106 und 10 Patienten mit I-125 bestrahlt. Ergebnisse. Die präoperative mittlere MAH betrug 5,2 mm [Standardabweichung (SA): 1,5 mm; Gruppe Ru-106: 5,7 mm (SA: 1,0 mm); Gruppe I-125: 5,0 mm (SA: 1,9 mm)]. Bei 11 Patienten (55%) (Ru-106: 5; I-125: 6) wurden präoperativ “Networks” in der ICGA identifiziert. Der Mittelwert der Tumorprominenzabnahme 1 Jahr nach Bestrahlung war bei Melanomen mit präoperativ nachweisbaren Networks 51,3% (SA: 14,7%) und bei Melanomen ohne nachweisbare “Networks” 28,0% (SA: 16,4%). Der Unterschied zwischen beiden Gruppen war statistisch signifikant (p=0,003, Mann-Whitney-Test). Es zeigte sich kein statistisch signifikanter Unterschied der Rückbildungsgeschwindigkeit zwischen den Melanomen, die mit Ru-106 bzw. I-125 bestrahlt worden waren (p=0,165, Mann-Whitney-Test). Schlussfolgerung. Rasch proliferierende Tumoren gelten im Allgemeinen als strahlensensitiv. Daraus erklärt sich auch die Beobachtung, dass Tumoren, die nach Brachytherapie eine schnellere Tumorrückbildung aufweisen, häufiger metastasieren. Auch histologisch nachweisbare “Networks” gelten als Zeichen eines aggressiven, metastasierenden Tumors. Diese “Networks” sind auch in der ICG-Angiographie darstellbar. Unsere Beobachtungen weisen auf einen Zusammenhang zwischen Tumorrückbildungsgeschwindigkeit und angiographischem Nachweis von “Networks” hin.AbstractIntroduction. The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates. Methods. We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradia-ted with Id-125. Results. The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p=0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p=0.165, Mann-Whitney test). Discussion. Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.

Results of Rhegmatogenous Retinal Detachment Repair in Cytomegalovirus Retinitis With and Without Scleral Buckling

PURPOSE To determine if scleral buckling is of any benefit in surgical repair of cytomegalovirus (CMV)-associated retinal detachment if combined with vitrectomy, silicone oil, and inferior midperipheral endolaser. MATERIALS AND METHODS Twenty-two consecutive eyes with CMV-associated retinal detachments were repaired with vitrectomy and endolaser to all breaks and to the inferior midperipheral retina using silicone oil without scleral buckling (group 1, control group) between July 1987 and May 1992. Results were compared with another series of 56 consecutive eyes undergoing vitrectomy, silicone oil injection, endolaser to all breaks, and 360 degrees encircling scleral buckling (group 2, study group) between June 1992 and July 1993. RESULTS Total retinal reattachment rates were 84% for group 1 and 86% for group 2. Rates of macular reattachment were 91% for group 1 and 91% for group 2. Mean best postoperative refracted visual acuity was 20/66 for group 1 and 20/67 for group 2. Median best postoperative refracted visual acuity was 20/74 for group 1 and 20/80 for group 2. These differences in results between the two groups were not statistically significant. Mean postoperative refractive error was +3.95 for group 1 and +4.92 for group 2. Patients who underwent surgery with the macula attached had a better postoperative visual outcome. CONCLUSION Scleral buckling may not be necessary in CMV-related retinal detachment if repaired with vitrectomy, silicone oil, and inferior midperipheral endolaser. Elimination of scleral buckling may reduce intraoperative time, patient morbidity, and the risk of an accidental needle stick. Patients with macula-on retinal detachments also should be considered for surgery before macular detachment.

Immune Predispositions for Cytomegalovirus Retinitis in AIDS: The HNRC Group

CMV retinitis develops in approximately 28-35% of all AIDS patients at later stages of disease, often leading to blindness. To determine whether the subset of AIDS patients who developed CMV retinitis (CMV-R) were immunologically predisposed, T cell proliferation responses to CMV were examined prospectively in an HIV infected, HLA typed, longitudinal study population. Individuals who developed CMV-R had significantly lower T cell proliferation responses to CMV, both early and late in disease, compared to CD4 matched controls who have not developed CMV-R. Since HLA proteins influence T-cell recognition, phenotypes of 21 CMV-R patients were examined to determine whether certain HLA alleles were associated with low immune response and predisposed AIDS patients to CMV-R. HLA DR7 and B44 were at increased (nearly twice the expected) frequency in those with CMV-R. The combined association of either B44, 51 or DR7 with CMV-R was highly significant (P = .008, relative risk of CMV-R = 15) with correction for multiple comparisons. Low immune responses were twice as frequent in those with (61%) compared to those without (30%) predisposing alleles. Thus, AIDS patients with immunogenetically related hyporesponsiveness to CMV antigens may be at increased risk of retinitis.