Carmen K. M. Chan

Cytotoxicity of Triamcinolone on Cultured Human Retinal Pigment Epithelial Cells: Comparison with Dexamethasone and Hydrocortisone

PurposeTriamcinolone acetonide (TA) is a corticosteroid that can be used in the treatment of cystoid macular edema (CME) and other ocular inflammatory conditions. This study aims to investigate the degree of cytotoxic effect of TA on human retinal pigment epithelium (ARPE19 cell line) and to compare the relative toxicity of TA with two other corticosteroids, hydrocortisone (HC) and dexamethasone (DEX), over a range of concentrations and durations of exposure.MethodsThe ARPE19 cell line was cultured and maintained in a 1:1 mixture of Dulbecco’s modified Eagle’s medium and HAMS F12 medium containing 3 mM l-glutamine supplemented with 10% fetal bovine serum, penicillin G, and streptomycin sulfate. Following an initial overnight incubation, corticosteroids (0.01–1 mg/ml) or vehicle (benzyl alcohol, 0.025%), diluted in culture medium, was added to the ARPE19 culture (5000 cells/well) on Day 0. Subsequently the culture medium containing corticosteroid or vehicle was refreshed daily. After 1, 3, and 5 days, the proliferated amount of cells with and without corticosteroid treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate, with n = 4 in all cases. The final results were analyzed using analysis of variance.ResultsTA, DEX, and HC caused a significant reduction in cell numbers throughout the whole range of concentrations when cells were exposed to them for more than one day. The action of the corticosteroids, apart from TA, was biphasic. There was an initial rise in cell proliferation in the presence of DEX and HC at 0.01–0.1 mg/ml on Day 1. Log-linear plots of DEX and HC concentrations against percent viability (mean % ± SD) showed a significantly higher total viable cell percentage versus TA: 120.5 ± 1.8% and 134.9 ± 4.1% in the presence of DEX, and 110.0 ± 15.3% and 118.3 ± 9.0% in the presence of HC. The LD50 values of the three corticosteroids show that, regardless of the duration of exposure, TA was the most toxic, with relative toxicity of TA > DEX > HC, equivalent to a ratio of 1.0 : 1.6 : 1.8, after one day of incubation. The vehicle alone had no effect.ConclusionsThe present study demonstrated the degree of cytotoxicity of TA compared with DEX and HC. The results provide a profile of this drug relative to other common corticosteroids. Further studies are planned to characterize its effects and the degree of influence on cells of different ocular regions in order to show the full cytotoxicity of TA.

Efficacy of 1.25 MG versus 2.5 MG intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial.

Purpose: To evaluate the efficacy of intravitreal injections of two different dosages of bevacizumab (Avastin) for treating diffuse diabetic macular edema. Methods: Fifty-two eyes of 52 patients with diabetic macular edema were randomized to receive three monthly intravitreal injections of 1.25 mg or 2.5 mg bevacizumab. Patients were observed for 6 months and optical coherence tomography central foveal thickness, logMAR best-corrected visual acuity (BCVA), and adverse events were assessed. Results: Forty-eight eyes of 48 patients completed the 6-month follow-up and were analyzed. Significant mean central foveal thickness reductions were observed in both groups at all follow-up visits (P < 0.013). Significant improvements between baseline and 6-month mean logMAR BCVAs were seen, with the mean logMAR BCVA improved from 0.63 to 0.52 in the 1.25 mg group and 0.60 to 0.47 in the 2.5 mg group. No significant difference in BCVA was observed between the two groups at any time point (P > 0.56). Subgroup analysis showed that intravitreal bevacizumab seemed to be more effective in eyes without any previous diabetic macular edema treatment. Conclusions: Three monthly intravitreal bevacizumab injections resulted in significant reduction in central foveal thickness and improvements in BCVA in diabetic macular edema patients. Both 1.25 mg and 2.5 mg seemed to have similar treatment efficacy.

Treatment of choroidal neovascularization in central serous chorioretinopathy by photodynamic therapy with verteporfin

PURPOSE To evaluate the safety and efficacy of photodynamic therapy (PDT) with verteporfin in the treatment of patients with choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSC). DESIGN Open-label, two-center, noncomparative, prospective interventional case series. METHODS Consecutive patients with subfoveal or juxtafoveal CNV secondary to CSC were recruited and treated with a standard regimen of PDT with verteporfin. At regular 3-month follow-up examinations, re-treatment was considered if fluorescein angiography showed evidence of leakage. Outcome measures included the proportion of patients who had improvement (gained 2 more lines), stable, or loss (dropped in 2 or more lines) in vision at the final follow-up and the changes in best-corrected visual acuity (BCVA) from baseline. RESULTS Ten eyes of 10 patients were recruited into the study. The mean age of the patients was 57.3 years with a mean follow-up duration of 12.6 months. At the last follow-up, six (60%) eyes gained 2 or more lines of BCVA with four (40%) patients having final BCVA of within 1 line. No patient lost 2 or more lines of BCVA. The mean logarithm of the minimal angle of resolution BCVA improvement after PDT was 2.4 lines (Wilcoxon signed-rank test, P =.013). No patient suffered serious ocular or systemic complications from PDT. CONCLUSIONS Photodynamic therapy with verteporfin therapy is a safe and well-tolerated treatment in patients with CNV associated with CSC. A randomized, controlled trial with a longer follow-up period is warranted to further study the efficacy of PDT in the management of CNV secondary to CSC.

Topical atropine in retarding myopic progression and axial length growth in children with moderate to severe myopia: a pilot study.

PurposeTo study the safety and efficacy of topical 1% atropine eye ointment in retarding myopic progression in children with moderate to severe myopia.MethodsThis was an interventional control study. Children (aged 5–10 years) with myopia of −3.00 diopters (D) or more were treated with 1% atropine ointment once daily for 1 year. Baseline and regular assessments of refractive errors by cycloplegic autorefraction and of axial length were done by ultrasound biometry, and the results were compared with data of control subjects.ResultsTwenty-three children (mean age: 7.4 ± 1.6 years) with moderate to severe myopia, being treated in the Hong Kong Eye Hospital of the Chinese University of Hong Kong, were recruited into the atropine group, and 23 children from the same eye clinic were matched with the study subjects with respect to age, sex, and initial spherical equivalent refraction, as controls. The initial refractive errors were −5.18 ± 2.05 D and −5.12 ± 2.33 D in the atropine and the control groups, respectively (P = 0.934). Myopic progression was significantly less (P = 0.005) in the atropine group (+0.06 ± 0.79 D) than in the control group (−1.19 ± 2.48 D). Axial length increase was also significantly smaller in the atropine group (0.09 ± 0.19 mm) than in the control group (0.70 ± 0.63 mm) (P = 0.004). One child (4.3%) developed an allergic reaction. No other major adverse effects related to the treatment were noted.ConclusionTopical 1% atropine ointment is a safe and effective treatment for retarding myopic progression in moderate to severe myopia. Further large-scale randomised controlled study with longer follow-up seems warranted. Jpn J Ophthalmol 2007;51:27–33

Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies

Background: The residual peripapillary retinal nerve fiber layer thickness (PRNFLT) corresponding to no light perception vision from long-standing nonglaucomatous optic neuropathies has not been documented. Such a benchmark would be useful information because PRNFLT is being used as an indicator of the visual recovery potential in patients with optic neuropathies. Methods: By means of optical coherence tomography (OCT) using a fast RNFL thickness protocol, we determined the PRNFLT in 8 patients with no light perception (NLP) for at least 1 year from acquired nonglaucomatous optic neuropathies. All patients underwent an assessment of visual acuity, color vision, visual field, pupillary reactions to light stimulation, and ophthalmoscopy. Results: Four of the 8 patients had a normal fellow eye. The average PRNFLT in the 4 normal eyes was 97.90 μm (range 94.82-100.89 μm), whereas the average PRNFLT in 8 of the 9 eyes with NLP was 45.42 μm (range 37.65-51.46 μm). Conclusions: Eyes with long-standing NLP vision from nonglaucomatous optic neuropathies retain a residual PRNFLT of about 45 μm as measured by OCT. This should be taken into consideration when using PRNFLT to assess visual prognosis in patients with poor vision from various optic neuropathies.

Phacoemulsification with intravitreal triamcinolone in patients with cataract and coexisting diabetic macular oedema: a 6-month prospective pilot study

AimsTo assess the safety and efficacy of phacoemulsification with intravitreal triamcinolone (ivTA) injection in diabetics with cataract and clinically significant macular oedema (CSMO).MethodsA total of 19 eyes of 15 consecutive diabetic patients with cataract and CSMO were prospectively recruited. Patients underwent phacoemulsification and intraocular lens implantation with 4 mg ivTA injection at completion of surgery. Patients were followed up on day 1, then weekly for 1 month, and thereafter monthly until 6 months postoperatively. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography, and adverse events were recorded.ResultsIn total, 17 eyes completed 6 months of follow-up. In all, 58.8% showed improvement in BCVA of ⩾2 lines, with statistically significant improvement in mean Snellen BCVA of 2.4 lines at 6 months. The peak BCVA was achieved at 4 months. The mean CMT decreased from a baseline of 449 μm to a minimum of 321±148 μm (28.5% reduction) achieved at 2 months, with statistically significant reduction at all postoperative time intervals until 6 months. Of 17 eyes, 4 (23.5%) developed transiently elevated intraocular pressure that normalised by 6 months in all but one patient. No injection- or surgery-related complications were encountered.ConclusionsPhacoemulsification with concurrent 4 mg ivTA injection appears to be a safe option for managing diabetics with cataract and CSMO. However, large-scaled randomised controlled trials are necessary for delineating the relative contributions of cataract removal and CMT reduction to visual improvement. Moreover, the transient effect on CMT may warrant further studies to determine optimal timing and dosage of further ivTA injections.

Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease

Purpose To evaluate the effects of the duration of oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada (VKH) disease.Methods Retrospective analysis of 35 VKH patients who received oral corticosteroid during the first attack of VKH with a minimum follow-up of 6 months. Patients were divided into two groups on the basis of the oral corticosteroid treatment duration of less than 6 months or 6 months or more. Kaplan–Meier survival and Cox-regression analyses were carried out to compare the recurrence rates of inflammation in the two groups.Results The mean age of onset was 42.5 years and the mean follow-up duration was 3.6 years. During the follow-up period, 10 (58.8%) of the 17 patients who received oral corticosteroid for less than 6 months compared with 2 (11.1%) of the 18 patients who had treatment for 6 months or more developed recurrence of inflammation (P=0.003). Cox-regression analysis showed that the duration of oral corticosteroid treatment for less than 6 months was the only significant risk factor for recurrence of VKH after adjustment for age, gender, and the initial dosage of oral corticosteroid treatment (adjusted odds ratio=8.8, P=0.008). Patients who received oral corticosteroid treatment for less than 6 months were also more likely to have one eye with visual acuity of 20/200 or worse (P=0.016).Conclusions Early withdrawal of oral corticosteroid is associated with increased risk of recurrence of VKH and worse visual prognosis. Oral corticosteroid should be tapered off slowly and maintained for at least 6 months for the treatment of acute VKH.

Intravitreal triamcinolone for diabetic macular oedema in Chinese patients: six-month prospective longitudinal pilot study

Aim: To evaluate the safety and efficacy of intravitreal triamcinolone (IVTA) in Chinese patients with diabetic clinical significant macular oedema (CSMO).

Ophthalmic manifestations and risk factors for mortality of HIV patients in the post‐highly active anti‐retroviral therapy era

Background:  To evaluate the ophthalmic manifestations and risk factors for mortality in HIV patients in the post‐highly active anti‐retrovirus therapy (HAART) era.

Quantitative assessment of optic nerve head morphology and retinal nerve fibre layer in non- arteritic anterior ischaemic optic neuropathy with optical coherence tomography and confocal scanning laser ophthalmoloscopy

Background/aims: To compare the optic disc parameters between patients with non-arteritic anterior ischaemic optic neuropathy (NAION) and normal controls, using optical coherence tomography (OCT) and Heidelberg Retinal Tomograph III (HRT), and to evaluate the structure–function relationship in NAION eyes. Methods: Both eyes of 22 patients with typical unilateral NAION of ⩾6 months’ duration and 52 eyes from 52 randomly selected normal subjects underwent Humphrey visual field (HVF) examination and measurement of optic disc and retinal nerve fibre layer thickness (RNFLT). Results: For the NAION-affected eyes, NAION fellow eyes and normal controls, the ocular magnification-corrected OCT disc areas were respectively 1.849 (SD 0.343) mm2, 1.809 (0.285) mm2 and 1.964 (0.386) mm2; the cup areas were 0.246 (0.187) mm2, 0.172 (0.180) mm2 and 0.469 (0.332) mm2. On HRT, the disc areas were 2.11 (0.38) mm2, 2.06 (0.40) mm2 and 2.16 (0.42) mm2; and the cup areas were 0.28 (0.34) mm2, 0.25 (0.18) mm2 and 0.48 (0.32) mm2. On both OCT and HRT, the cup areas and cup–disc area ratios (CDAR) of both eyes of NAION patients were significantly smaller than controls (p⩽0.01), but the disc areas were not (p⩾0.21). There was a significant correlation between HVF mean deviation and OCT RNFLT (r = 0.44, p = 0.04) but not with HRT RNFLT (p = 0.30) in NAION-affected eyes. Conclusion: NAION patients have smaller optic cups and CDARs in both eyes compared with controls. A larger sample size is necessary to demonstrate if disc size affects the risk of developing NAION. The NAION-affected eyes’ OCT RNFLT correlated with HVF mean deviation but the HRT RNFLT did not.