Nuttawut Rodanant

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

PURPOSE To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment. DESIGN Randomized controlled clinical trial. METHODS Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes. RESULTS Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes. CONCLUSIONS Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.

Preventive Versus Treatment Effect of Ag3340, a Potent Matrix Metalloproteinase Inhibitor in a Rat Model of Choroidal Neovascularization

PURPOSE AG3340 (prinomastat) is a nonpeptidic, small-molecular-weight, synthetic matrix metalloproteinase inhibitor (MMPI) with selective inhibitory action of MMP-2, MMP-9, MMP-3, and MT-MMP1. We evaluated AG3340 injected intravitreally to treat choroidal neovascularization in a laser induced rat CNV model. METHODS In the pretreatment group, the drug was injected the same day after induction of choroidal neovascularization by diode laser. In the treatment group, the drug was injected 2 weeks after induction of choroidal neovascularization (CNV). Fluorescein and indocyanine green angiography were performed to evaluate CNV. ERG recordings and histology were performed to assess toxicity and the CNV lesions. RESULTS When used at the time of CNV induction, 62.8% of lesions in control versus 22.8% of the laser lesions in treated eyes developed CNV (p < 0.0001). The invading fibrovascular complex was thicker in the control eyes than that in the treated eyes. No signs of toxicity were detected. When used to treat established CNV, the percentage of leakage in treated and control eyes were 54.1% and 58.9% respectively (p > 0.05). Prinomastat was effective when given at the time of induction of CNV in the rat model. Administration of prinomastat 2 weeks after laser induction did not show efficacy. CONCLUSION Prinomastat was active in the earliest stages of experimental CNV. It might be best used in combination with photodynamic therapy to inhibit recurrence of CNV from temporarily closed new vessels.

Effect of subthreshold infrared laser treatment for drusen regression on macular autofluorescence in patients with age-related macular degeneration.

Background: Subthreshold laser therapy has been shown to cause drusen reduction. Using this method, visible laser burns are not created in the retina; presumably, the energy is absorbed by the retinal pigment epithelium (RPE) and stimulates reabsorption of drusen material, sparing photoreceptors from destruction. We hypothesized that autofluorescence (AF) changes would be visible after such treatment and might be sensitive to quantify RPE changes. Methods: Twenty eyes of 13 patients with nonexudative age-related macular degeneration were studied. Forty-eight subthreshold infrared diode laser spots were applied as treatment to cause drusen regression. Before, immediately after, and 3 months after treatment, color fundus photography, fluorescein angiography (FA), and autofluorescence (AF) imaging were performed. Treated lesions were identified on overlay images of all three imaging methods. Results: The averaged sensitivity of AF imaging compared with FA was 29.6 ± 28.7% versus 10.2 ± 12.2% (P = 0.008) at the immediate posttreatment time point and 43.5 ± 28.7% versus 33.8 ± 26.5% (P = 0.043) at the 3-month posttreatment time point, respectively. Reduction of drusen at 3 months correlated with the detection sensitivity of AF imaging at the immediate posttreatment time point (P = 0.022). Conclusion: Immediately after subthreshold laser treatment, AF imaging was more sensitive to detect RPE changes than FA. This suggests that noninvasive AF imaging may allow prediction of the effect of subthreshold laser treatment and might be used to titrate treatment dose.

Ganciclovir release rates in vitreous from different formulations of 1-O-hexadecylpropanediol-3-phospho-ganciclovir.

PURPOSE To determine the optimal formulation of lipid prodrug, 1-O-hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV), for intravitreal delivery. METHODS Equal concentrations of crystalline or liposomal HDP-P-GCV were exposed to rabbit whole vitreous, core vitreous, peripheral vitreous, human plasma, and heat inactivated rabbit vitreous, and the samples were incubated at 37 degrees C for one week. Aliquots were taken at day 1, 2, 3, and 7 and subjected to HPLC analysis for conversion to GCV. RESULTS The resultant concentration of GCV from crystalline HDP-P-GCV in vitreous was 198 +/- 49 microM (n = 3) at day 1 and 1253 +/- 248 microM (n = 3) at day 7. The resultant concentration of GCV from the liposomal formulation of HDP-P-GCV in vitreous was much lower, yielding a concentration of 66 +/- 7 microM (n = 3) at day 1 and 243 +/- 39 microM (n = 3) at day 7 (P < 0.001, t Test). When the crystalline HDP-P-GCV was incubated with heat-inactivated vitreous, the detectable GCV concentrations were low (22 microM) and did not increase over time. The concentration of GCV detected from the crystalline HDP-P-GCV in the core vitreous was 19.69 +/- 3.84 microM (n = 3) at day 1 and 1537.36 +/- 177.14 microM (n = 3) at day 7. The concentration of GCV released from crystalline HDP-P-GCV in peripheral vitreous was 32.86 +/- 5.07 microM (n = 3) at day 1 and 1805.78 +/- 327.94 microM (n = 3) at day 7. Detectable GCV concentration from both core and peripheral vitreous samples increased over time, however, the magnitude of GCV release from peripheral vitreous samples was higher (P < 0.05, t Test). CONCLUSION In vitreous, HDP-P-GCV as a crystalline formulation was converted to GCV more rapidly than liposomal formulation of HDP-P-GCV. Vitreous cells may play an important role in the metabolism of either formulation of HDP-P-GCV delivered into vitreous.

Surgical outcomes of preoperative steroid for rhegmatogenous retinal detachment with associated choroidal detachment

PurposeTo investigate the effect of preoperative steroid on anatomical and functional outcomes of vitrectomy in patients with rhegmatogenous retinal detachment with associated choroidal detachment (RRD-CD), a rare but particular type of RRD.Patients and methodsThis retrospective cohort study included RRD-CD patients at Siriraj Hospital during January 2005 to December 2014. Patients with preexisting uveitis or RRD with giant retinal tears were excluded. Preoperative, intraoperative, and postoperative data were reviewed and analyzed.ResultsA total of 76 patients (76 eyes) with RRD-CD were included: 37 patients without preoperative steroid (Group A) and 39 patients with preoperative steroid for a median of 7 days (Group B: 34 patients with oral prednisolone (0.5–1 mg/kg/day) and 5 patients with 20 or 40 mg of subtenon triamcinolone). The total retinal reattachment rate at 3 months after one operation was not different between the two groups (59 vs 51%) with adjustment for confounders. The proportion of patients with visual acuity (VA) improvement at 3 months was also not different (57 vs 54%). Survival analysis revealed that 96% of redetachment cases occurred within the first 3 months and redetachment rate was not different between the two groups for up to 3 years. However, Group B showed a significant regression (partial or complete) of CD prior to operation compared to Group A (82 vs 30%, P<0.001).ConclusionPreoperative steroid significantly improved CD before vitrectomy, but seemed not to improve the single-operation retinal reattachment rate or VA at 3 months when compared to no steroid treatment in RRD-CD patients.

Autofluorescence image in ocular albinism.

AUTOFLUORESCENCE IMAGE IN OCULAR ALBINISM A 46-year-old patient had nystagmus and poor vision in both eyes and normal skin and hair color since birth. Two of his male cousins on his mother’s side had the same history. His visual acuity was 20/300 in the right eye and 20/400 in the left. Ophthalmoscopically, iris transillumination defects, a blond fundus with the absence of a foveal pit and luteal pigment, absence of the normal hyperpigmentation of the foveal pigment epithelium, and prominent retinal vessels coursing through the putative macular area instead of arching around it 1 were observed in both fundi (Figure 1). Fluorescein angiography showed prominent choroidal vasculature (Figure 2). An autofluorescence image of the fundus showed absence of the blockage of autofluorescence in the foveal area (Figure 3). Scanning laser ophthalmoscopy 2 has been used to image fundus autofluorescence derived from lipofuscin granules within the retinal pigment epithelium (RPE) cells in many hereditary and degenerative retinal diseases.3,4 Accumulation of lipofuscin in the RPE is mainly from the incomplete degradation of phagocytosed distal outer segments of photoreceptors. By using an argon blue laser (488 nm) to scan the retinal surface for excitation, the emitted light from lipofuscin is collected through a 500-nm barrier filter and detected confocally using a commercially available confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Carlsbad, CA). In the normal fundus (Figure 4), the foveal pigment epithelium area shows less autofluorescence because the overlying retinal xanthophyll absorbs the short-wavelength light. In addition, there may be a lower RPE lipofuscin concentration in this area. 5 In autofluorescence images, retinal vessels appear dark due to blockage of RPE autofluorescence. To our knowledge, our case is the first report of autofluorescence imaging results in ocular albinism. The absence of hypoautofluorescence in the fovea is due to the lack of luteal pigment in the area of foveal hypoplasia.