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Purpose We investigated whether zinc dyshomeostasis, a known mechanism of cell death in acute brain injury, contributes to the activation of matrix metalloproteinases (MMPs) and photoreceptor cell death in experimental retinal detachment (RD). Methods RD was induced in mice by subretinal injection of 1:1 mixture of balanced salt solution and 1% sodium hyaluronate. On days 1 and 3 post RD, eyeballs were sectioned and examined for cell death (TUNEL staining), the degree of hypoxic insult (Hypoxyprobe staining), free zinc levels (TFL-Zn staining), and MMP-2 and -9 activity (gelatin zymography). In addition, we examined whether modulating extracellular zinc concentration or MMP activation in subretinal fluid affected photoreceptor cell death in RD. These changes were further examined in primary retinal cell and photoreceptor-derived cell (661W) cultures. Results Photoreceptor cell death peaked on day 3 post RD. Intracellular zinc markedly decreased on day 1 post RD, and subsequently accumulated on day 3. MMP-2 and -9 activity showed a concurrent increase in detached retinas. Detached retinas stained with Hypoxyprobe showed strongly positive cells, especially in the photoreceptor layer. Subretinal injection of a zinc-chelator (CaEDTA) or MMP inhibitor (GM6001, minocycline) at the time of RD significantly attenuated photoreceptor cell death in RD. Similar findings were confirmed in oxygen-glucose-deprived or zinc-exposed cell cultures. Conclusions Upon RD, hypoxic retinal cells in deep layers underwent zinc dyshomeostasis, MMP activation, and ultimately death. These findings provide new insight into the possible mechanism of photoreceptor death in RD, and as such may prove useful in crafting protective measures for photoreceptor cells.

PURPOSE To analyze differences in ultra-widefield fluorescein angiography (UWFFA) findings between patients with recurrent postvitrectomy diabetic vitreous hemorrhage (PVDVH) and patients with non-PVDVH (NPVDVH). METHODS Patients were categorized as PVDVH when vitreous hemorrhage recurred after diabetic vitrectomy. Age-matched control diabetic patients in whom vitreous hemorrhage did not recur after vitrectomy were assigned to the NPVDVH group. Baseline characteristics were compared between groups. Also peripheral angiographic findings such as peripheral neovascularization, nonperfusion, and late peripheral vascular leakage were analyzed by UWFFA. RESULTS A total of 46 eyes were included this retrospective study: 22 with PVDVH and 24 with NPVDVH. Preoperative, 3-month postoperative, and final-visit best corrected visual acuity (BCVA) were not different between the two groups. The rate of peripheral neovascularization was significantly different (PVDVH 40.9%, NPVDVH 8.3%, P = 0.010). The rate of peripheral nonperfusion was significantly greater in PVDVH eyes than in NPVDVH eyes (81.8% vs. 37.5%, P = 0.002). The rate of late peripheral vascular leakage was also significantly greater in PVDVH eyes (90.9% vs. 29.2%, P < 0.001). These differences in peripheral angiographic findings were not seen within the conventional Early Treatment Diabetic Retinopathy Study (ETDRS) 7 standard fields. Ischemic index was also significantly higher in the PVDVH group than in the NVDVH group. CONCLUSIONS Compared with diabetic vitrectomized eyes that did not have recurring vitreous hemorrhage, PVDVH eyes had a higher rate of peripheral neovascularization, nonperfusion, and late peripheral vascular leakage. These differences were not found within the conventional ETDRS 7 standard fields. Therefore, it is important to assess peripheral retinal vessels by UWFFA after diabetic vitrectomy. Furthermore, in cases of peripheral neovascularization, peripheral nonperfusion, and late peripheral vascular leakage, additional treatment may be necessary to prevent PVDVH.

PURPOSE: To evaluate the characteristics of spectral-domain optical coherence tomography (SD-OCT) findings associated with visual outcome and compare OCT measurements according to presence of cystoid macular edema (CME) in retinitis pigmentosa (RP) patients. METHODS: Patients with typical RP who underwent SD-OCT were included. We compared OCT measurements such as central retinal thickness (CRT), photoreceptor thickness, and photoreceptor inner segment/outer segment (IS/OS) junctional status at the fovea between the CME and non-CME groups. Also, correlations between best-corrected visual acuity (BCVA) and each parameter were determined. RESULTS: Among a total of 220 eyes in 128 RP patients, 46 eyes of 30 patients (20.9%) had CME. CRT was 303.1 ± 81.8 μm and 209.2 ± 46.8 μm in the CME and non-CME groups, respectively (P < 0.001). BCVA did not differ between the two groups (P = 0.690). However, among a subgroup with unilateral CME, BCVA was significantly worse in CME eyes than in the fellow eyes (P = 0.046). In the CME group, eyes with increased CRT showed worse BCVA (P = 0.010). Among 12 eyes with severe CME, defined as 350 μm or more CRT, 10 (83.3%) showed an absent IS/OS junction. In the non-CME group, in contrast, eyes with decreased CRT showed worse BCVA (P < 0.001). In both groups, severe IS/OS disruption was correlated with worse BCVA (P < 0.001). The risk of IS/OS disruption was higher in the CME group (P = 0.016). CONCLUSIONS: The presence of CME in RP patients was not necessarily correlated with loss of visual acuity. In eyes with CME, however, severe CME was strongly correlated with IS/OS disruption and visual impairment. Thus, severe CME seemed to be a predictor of poor visual outcome in RP patients.

PURPOSE To evaluate the glaucoma progression in patients with a history of refractive corneal surgery (RCS). METHODS A total of 313 eyes of 313 glaucoma patients (RCS group, 34 eyes; non-RCS group, 279 eyes) with a mean follow-up period of 2.7 years were included. Glaucoma progression was determined either by experts' stereoscopic optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. Uni- and multivariate Cox's proportional hazards models were used to determine associations between potential risk factors including a history of RCS and glaucoma progression. RESULTS Among 313 eyes, 87 (27.8%) eyes showed progression either by optic disc/RNFL photographs or VF assessment during the follow-up period. Ten (29.4%) of eyes in the RCS group and 77 (27.6%) of eyes in the non-RCS group showed glaucoma progression; however, prevalence of progression did not differ between the two groups (P = 0.482). Among all participants, baseline age and VF pattern standard deviation (PSD; hazard ratios of 1.013 and 1.119; P = 0.026 and P < 0.001, respectively) were significant risk factors for progression. In both the RCS and the non-RCS group, only VF PSD was a significant risk factor for progression according to multivariate Cox proportional hazards (1.193, 1.099, P < 0.001, P < 0.001, respectively). CONCLUSIONS Baseline VF PSD and age substantially affected glaucoma progression in all study participants, although their RCS history was not a significant risk factor for glaucoma progression.

PURPOSE. To evaluate and compare the glaucoma discrimination ability of macular inner retinal layer (MIRL) thickness with that of peripapillary retinal nerve fiber layer (pRNFL) thickness measured by spectral-domain optical coherence tomography (RTVue-100; Optovue Inc, Fremont, CA) in patients with normal-tension glaucoma (NTG). METHODS. Sixty-five healthy subjects and 102 with NTG were enrolled. MIRL thickness provided by a ganglion cell complex (GCC) scan and two RNFL thicknesses measured by the NHM4 (RNFL1) and RNFL 3.45 (RNFL2) modes of the RTVue-100 system were analyzed. The areas under the receiver operating characteristic curves (AUCs) of MIRL and pRNFL thicknesses for discriminating patients with NTG from control subjects were determined. The AUCs were compared between patients with central visual field (VF) defects (VF; 10° of fixation) and peripheral VF defects (10° from fixation). RESULTS. The average MIRL thickness showed a strong correlation with both RNFL1 and -2 thicknesses (R 2 0.773, 0.774, both P 0.0001). The AUCs for average MIRL, RNFL1, and RNFL2 thicknesses were not significantly different at 0.945, 0.973, and 0.976, respectively. However, the AUCs of the average and superior MIRL thicknesses were significantly less than that of the pRNFL thickness in eyes with moderate-toadvanced glaucoma and eyes with peripheral VF defects. CONCLUSIONS. The average MIRL thickness showed a strong correlation with pRNFL thickness, because patients with NTG at an early stage showed paracentral VF defects near the fixation point. MIRL thickness showed glaucoma discrimination ability comparable to that of pRNFL thickness in patients with NTG with early VF defects. In eyes with advanced or peripheral VF defect, pRNFL measurement showed a better glaucoma diagnostic ability than did MIRL measurement. (Invest Ophthalmol