Andre Messias

Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study

PURPOSE To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP). METHODS Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan. RESULTS TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group. CONCLUSIONS TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.).

Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial.

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 × 106 autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 μV), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 μV) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies.

Intraocular lens power calculation and optimized constants for highly myopic eyes

PURPOSE: To determine the accuracy of intraocular lens (IOL) power calculations in eyes with high myopia and to suggest adjusted constants for these cases. SETTING: Centre for Ophthalmology, Eberhard‐Karls‐University, Tuebingen, Germany. METHODS: Patients with high myopia having phacoemulsification with implantation of an AcrySof MA60MA IOL (power range +5.00 to −5.00 diopters [D]) were evaluated. Optical biometry (IOLMaster) and IOL calculations were performed before and after IOL implantation. Because of different optic principal planes of negative‐diopter and positive‐diopter IOLs, separate constants were calculated for these groups. RESULTS: Fifty eyes (32 patients) were evaluated. Thirty eyes (mean AL 31.15 mm ± 1.69 [SD]) had implantation of a positive‐diopter IOL (mean power +3.10 ± 1.50 D) and 18 eyes (mean AL 33.20 ± 2.25 mm), a negative‐diopter IOL (mean power −3.20 ± 1.70 D). Postoperatively, the mean spherical equivalent was −1.42 ± 1.33 D and −0.41 ± 1.81 D, respectively. The difference in optimized constants between positive‐ and negative‐diopter IOLs was significant for all formulas. Power calculation with the SRK II formula showed a wide range of deviation of postoperative refraction from target refraction. Calculation with the Haigis, SRK/T, Holladay 1, and Hoffer Q formulas showed a mean deviation of 0.00 D with an SD of 0.88, 0.92, 1.03, and 1.15, respectively. CONCLUSIONS: Results indicate that the SRK II formula cannot be recommended for IOL power calculation in highly myopic patients. With optimized constants, the SRK/T, Haigis, Hoffer Q, and Holladay 1 formulas produced small deviation of postoperative refraction from target refraction.

Quantifying fixation in patients with Stargardt disease

Fixational eye movements in 60 eyes of 30 patients with ABCA4-associated Stargardt disease were recorded by a Scanning Laser Ophthalmoscope (SLO). The results were quantified by two new fixation quality measures expressing the eccentricity of the preferred retinal locus (PRL) non-parametrically, and fixation stability by a dynamic index. 46 eyes (77%) fixated eccentrically; in 32 eyes (70% of the eccentrically fixating eyes) the PRL was located above the central retinal lesion. PRL eccentricity correlated positively with logMAR visual acuity (r=.72; p<.0001) and negatively with fixation stability (r=-.58; p<.0001). Multiple PRL were found only in three eyes.

A prospective randomized trial of intravitreal bevacizumab versus ranibizumab for the management of diabetic macular edema.

PURPOSE To compare visual acuity and spectral-domain optical coherence tomography (SDOCT) outcomes associated with intravitreal (IV) bevacizumab vs IV ranibizumab for the management of diabetic macular edema (DME). DESIGN Prospective randomized trial. METHODS Forty-eight patients (63 eyes) with center-involved DME were randomly assigned to receive 1.5 mg (0.06 cc) IV bevacizumab or 0.5 mg (0.05 cc) IV ranibizumab at baseline and monthly if central subfield thickness was greater than 275 μm. RESULTS Forty-five patients (60 eyes) completed 48 weeks of follow-up. At baseline, mean ± standard error best-corrected visual acuity (BCVA) (logMAR) was 0.60 (20/80) ± 0.05 in the IV bevacizumab group and 0.63 (20/85) ± 0.05 in the IV ranibizumab group. A significant improvement in mean BCVA was observed in both groups at all study visits (P < .05); this improvement was significantly greater in the IV ranibizumab group compared with the IV bevacizumab group at weeks 8 (P = .032) and 32 (P = .042). A significant reduction in mean central subfield thickness was observed in both groups at all study visits compared with baseline (P < .05), with no significant difference in the magnitude of macular thickness reduction between groups. The mean number of injections was significantly higher (P = .005) in the IV bevacizumab group (9.84) than in the IV ranibizumab group (7.67). CONCLUSIONS IV bevacizumab and IV ranibizumab are associated with similar effects on central subfield thickness in patients with DME through 1 year of follow-up. IV ranibizumab is associated with greater improvement in BCVA at some study visits, and the mean number of injections is higher in the IV bevacizumab group.

Effect of +3.00 diopter and +4.00 diopter additions in multifocal intraocular lenses on defocus profiles, patient satisfaction, and contrast sensitivity

PURPOSE: To evaluate the advantages and disadvantages of the new low‐addition (add) (+3.00 diopter [D]) ReSTOR multifocal IOL compared with the preceding ReSTOR model with +4.00 D add. SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Comparative case series. METHODS: Patients with a +3.00 D or +4.00 D add multifocal IOL were examined for uncorrected and distance‐corrected visual acuity at distance, intermediate, and near. A defocus profile was assessed, individual reading distance and the distance for lowest intermediate visual acuity were determined. Patient satisfaction was evaluated with a standardized questionnaire. Contrast sensitivity was tested under mesopic and photopic conditions. RESULTS: Uncorrected and distance‐corrected intermediate visual acuities were statistically significantly better in the +3.00 D add group (24 eyes) than in the +4.00 D add group (30 eyes); distance and near visual acuities were not different between groups. The defocus profile significantly varied between groups. The +4.00 D add group had a closer reading distance (33.0 cm) than the +3.00 D add group (43.5 cm), a closer point of lowest intermediate visual acuity (65.8 cm versus 86.9 cm) and worse lowest intermediate visual acuity (20/59 ± 4.5 letters [SD] versus 20/48 ± 5.5 letters). Thus, patients in the +3.00 D add group reported being more satisfied with intermediate visual acuity. The +3.00 D add group reported more glare but less halos than the +4.00 D add group; contrast sensitivity was not different. CONCLUSION: The lower addition resulted in a narrower defocus profile, a farther reading distance, and better intermediate visual acuity and thus increased patient satisfaction. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.

Panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab for high-risk proliferative diabetic retinopathy

Purpose:  To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal injection of 0.5 mg of ranibizumab (IVR) in patients with high‐risk proliferative diabetic retinopathy (PDR).

Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness.

Background The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO2 or HR. Conclusions/Significance Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.

In vivo toxicity study of rhodamine 6G in the rat retina.

PURPOSE To investigate the intraocular effect of rhodamine 6G (R6G) on retinal structures and function in an in vivo rat model and to develop an in vivo method for accurate evaluation of new dyes for intraocular surgery. METHODS R6G in physiologic saline solution (PSS) was injected into the vitreous of adult Brown Norway rats at concentrations of 0.0002%, 0.002%, 0.02%, 0.2%, and 0.5%. Control animals received only PSS. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts, light microscopy 7 days later, photopic electroretinography (ERG), and measurement of scotopic sensitivity and recovery of dark adaptation 48 hours and 7 days after intravitreous injection. RESULTS R6G at concentrations of 0.2% and 0.5% led to a dose-dependent loss of RGC. The most significant loss occurred at 0.5%. Lower concentrations (0.0002%, 0.002%, and 0.02%) produced no statistically significant retinal ganglion cell loss. Analysis of the eyes by light microscopy showed no structural changes in the central retina, although injections of 0.5% R6G were followed by impressive degenerative changes adjacent to the injection sites. ERGs showed no effects of the highest R6G concentration on rods, kinetics of rhodopsin recovery after bleaching, or cone-driven responses. CONCLUSIONS R6G can be safely injected in doses of up to 0.02% in rats, but has a toxic effect on retinal ganglion cells at higher concentrations. Accumulation of R6G may be a problem at higher concentrations, particularly at the injection site.

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD

BackgroundPatients with early age-related maculopathy (ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD).MethodsTesting of the central visual field (8° radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63;20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n = 12), or early signs of ARM (eARM; n = 27) were examined. Performance was expressed summarily as a “field score” (FS).ResultsPerformance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels.ConclusionUsing parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.