Walter Yukihiko Takahashi

Enhanced depth imaging optical coherence tomography in long-standing Vogt–Koyanagi–Harada disease

Aim To evaluate the choroidal thickness (CT) in patients with long-standing Vogt–Koyanagi–Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods A prospective case–control study developed at a tertiary centre at São Paulo, Brazil. EDI-OCT images were obtained in 16 patients (30 eyes) with VKH disease who had had the disease for more than 6 months since disease onset, and in 17 normal individuals controlled by age (32 eyes). Comprehensive ophthalmic examination and EDI-OCT evaluation were performed. CT was measured at the fovea and at 1000 µm intervals from the foveal centre in both temporal and nasal directions. CT was correlated with disease duration, clinical disease activity and fundus-based disease severity. Results Mean subfoveal CT was 333 µm (±85.8) in controls and 250.7 µm (±93.3) in VKH patients (p=0.002). The choroid was significantly thinner in patients when compared to controls in all but one nasal point. In patients, the CT measurements at the foveal centre presented a negative correlation with disease duration (p<0.001). No significant difference in CT measurements was observed between eyes with and without clinical inflammation (p=0.42). There was a trend towards more severe fundus changes being associated with a thinner choroid (p=0.28). Conclusions Patients with VKH and long-standing disease had thinner choroids when compared to controls. Progressive choroidal thinning related to disease duration was observed at the macula of these patients. Whether this finding is part of the natural history of the disease or the result of a clinically undetected choroidal inflammation remains to be determined.

Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy and Macular Edema: One-year Results of a Randomized Clinical Trial

PURPOSE To evaluate laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). DESIGN Randomized clinical trial. METHODS settings: Single center. study population: Twenty-two patients with bilateral treatment-naïve moderate PDR and CSME. intervention: Laser (panretinal and macular) photocoagulation was performed in each eye, followed by IVTA in one randomly assigned eye. Best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography were performed at baseline and at months 1, 3, 6, 9, and 12. main outcome measures: Changes in BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser-only group (controls) at all study follow-up visits (P < .001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12 (20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months (P < .001). The mean CMT and TMV were, respectively, 360 microm and 8.59 mm(3) for the IVTA group and 331 microm and 8.44 mm(3) for the controls at baseline, and 236 microm and 7.32 mm(3) for the IVTA group and 266 microm and 7.78 mm(3) for the controls at 12 months (P < .001). CONCLUSIONS The combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME.

Mitomycin C as Adjunctive Therapy With Glaucoma Implant Surgery

Twenty-one eyes of 21 patients with refractory glaucoma underwent glaucoma surgery involving placement of a modified Molteno implant and intraoperative application of mitomycin C. Sixteen eyes (76.2%) had an intraocular pressure (IOP) of 21 mm Hg or less after a mean follow up of 9.4 +/- 6.4 months; additional medication was needed in six eyes. Major complications included early flat anterior chamber (42.9%), implant plate erosion (9.5%), tube erosion (4.8%), late hypotony (4.8%), tube-corneal touch (4.8%), and phthisis bulbi after choroidal hemorrhage (4.8%). Only one patient had a high IOP due to decreased filtration through the implant. These results suggest that glaucoma implant surgery with the adjunctive use of mitomycin C may be useful in eyes with refractory glaucoma.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi- Harada disease: a cross-sectional study

BackgroundTo investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy.MethodsTwenty-eight patients (51 eyes) with long-standing (≥6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis.ResultsDisease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes).ConclusionICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Quality of life in patients with age-related macular degeneration with monocular and binocular legal blindness

OBJECTIVE To evaluate the quality of life for persons affected by age-related macular degeneration that results in monocular or binocular legal blindness. METHODS An analytic transversal study using the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was performed. Inclusion criteria were persons of both genders, aged more than 50 years old, absence of cataracts, diagnosis of age-related monocular degeneration in at least one eye and the absence of other macular diseases. The control group was paired by sex, age and no ocular disease. RESULTS Group 1 (monocular legal blindness) was composed of 54 patients (72.22% females and 27.78% males, aged 51 to 87 years old, medium age 74.61 +/- 7.27 years); group 2 (binocular legal blindness ) was composed of 54 patients (46.30% females and 53.70% males aged 54 to 87 years old, medium age 75.61 +/- 6.34 years). The control group was composed of 40 patients (40% females and 60% males, aged 50 to 81 years old, medium age 65.65 +/- 7.56 years). The majority of the scores were statistically significantly higher in group 1 and the control group in relation to group 2 and higher in the control group when compared to group 1. CONCLUSIONS It was evident that the quality of life of persons with binocular blindness was more limited in relation to persons with monocular blindness. Both groups showed significant impairment in quality of life when compared to normal persons.

Testing intravitreal toxicity of rapamycin in rabbit eyes

PURPOSE To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 microg, 50 microg, 200 microg, and 1000 microg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 microg. Histological results showed no retinal toxicity in all groups. CONCLUSION Although ERG changes were identified at dosages between 50-1000 microg, the histology of all groups up to 1000 microg did not show any discernable abnormalities.

Toxicity of high-dose intravitreal adalimumab (Humira) in the rabbit.

PURPOSE To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye. METHODS Thirty New Zealand albino rabbits received intravitreous injections of 0.5 mg (6 eyes), 1.0 mg (6 eyes), 2.5 mg (6 eyes), 5 mg (6 eyes), and 10 mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. RESULTS Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5 mg. In the 10 mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5 mg, but there was a significant decrease in the photopic-wave ERG response in the 10 mg group (P=0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10 mg of adalimumab. CONCLUSIONS Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5 mg dose. In the 10 mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity.

Structural and Functional Assessment of Macula in Patients with High-Risk Proliferative Diabetic Retinopathy Submitted to Panretinal Photocoagulation and Associated Intravitreal Bevacizumab Injections: A Comparative, Randomised, Controlled Trial

Purpose: To compare the efficacy of therapy with panretinal photocoagulation (PRP) and intravitreal bevacizumab (IVB) injections versus PRP alone in patients with high-risk proliferative diabetic retinopathy (HR-PDR) with a 6-month follow-up. Methods: Forty-two patients with HR-PDR were prospectively studied in a randomised, masked, controlled trial. Both eyes of each patient were randomised either to the study group (SG) receiving PRP plus IVB injections or the control group (CG) receiving PRP alone. Mean change in visual acuity (VA), optical coherence tomography-measured foveal thickness (FT) and macular volume (MV) were compared. Results: Intergroup comparisons showed no significant difference in VA while FT exhibited a significant (p < 0.05) difference at 1 month of follow-up and MV was significantly reduced at the 1- and 3-month follow-up. Compared to baseline, VA was significantly worse at all follow-ups in the CG and was stable in the SG. FT increased significantly in the CG from baseline to the 1- and 6-month follow-ups and in the SG, no significant difference was observed. MV was significantly increased in the CG during all follow-up periods. Conclusion: In HR-PDR, using IVB injections as adjuvant treatment to PRP reduces the VA deterioration and results in decreased FT and MV measurements compared to PRP alone.

The Effects of Commercially Available Preservative-Free FDA-Approved Triamcinolone (Triesence®) on Retinal Cells in Culture

PURPOSE To evaluate the effects of Triesence® (TRI), a new preservative-free triamcinolone approved by the U.S. Food and Drug Administration (FDA) for intraocular use, on human retina pigment epithelial (ARPE-19) and rat neurosensory (R28) cells in culture. METHODS ARPE-19 and R28 cell cultures were treated 24 h with 1,000, 500, 200, or 100 μg/mL of crystalline (cTRI) or 1,000, 500, or 200 μg/mL of solubilized (sTRI). TRI was solubilized by centrifuging the drug, discarding the supernatant containing the vehicle and then resuspending the drug pellet in an equivalent amount of Dimethyl sulfoxide to achieve the same concentration as the commercial preparation. Percentage of cell viability (CV) was evaluated by a trypan blue dye-exclusion assay. The mitochondrial membrane potential (ΔΨm) was analyzed with the JC-1 assay. The caspase-3/7 activity was measured by a fluorochrome assay. RESULTS In the ARPE-19 cultures, the cTRI caused a decrease in CV at 1,000 μg/mL (13.03±6.51; P<0.001), 500 μg/mL (28.87±9.3; P<0.001), 200 μg/mL (54.93±5.61; P<0.001), and 100 μg/mL (82.53±0.65; P<0.005) compared with the untreated controls (96.98±0.16). In R28 cultures, the cTRI treatment also reduced CV values significantly (P<0.001) for the 1,000 μg/mL (22.73±2.44), 500 μg/mL (34.63±1.91), 200 μg/mL (58.70±1.39), and 100 μg/m (75.33±2.47) compared with the untreated controls (86.08±3.54). Once the TRI was solubilized (sTRI), the CV and ΔΨm remained similar to the untreated controls for both ARPE-19 and R28 cells. The sTRI treatment with 1,000, 500, and 200 μg/mL increased in caspase-3/7 activity in ARPE-19 cells (P<0.01) and in R28 cells (P<0.05) compared with dimethyl sulfoxide equivalent controls. CONCLUSION The crystalline form of TRI (cTRI) can cause a significant decrease in CV to cultured retinal cells. Once the TRI is solubilized (sTRI), at the same concentrations, the cells remain viable with no decrease in CV or ΔΨm. The sTRI can, however, increase caspase-3/7 activity, thus suggesting some degree of apoptosis.

A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy.

Purpose: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non–high-risk proliferative diabetic retinopathy. Methods: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. Results: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (−47.6 &mgr;m, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 &mgr;m (P = 0.001) in the SG and decreased by 45.5 &mgr;m (P = 0.11) in the CG. Conclusion: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non–high-risk proliferative diabetic retinopathy and diabetic macular edema.