PurposeThe purpose of this study was to compare 27-gauge (27G) with 25-gauge (25G) microincision vitrectomy in patients with epiretinal membrane (ERM).ParticipantsSeventy-four eyes of 66 patients undergoing 3-port pars plana vitrectomy using 27G or 25G instrumentation.MethodsSeventy-four eyes of 66 patients with ERM, who underwent 27G or 25G microincision vitrectomy were prospectively evaluated.ResultsThe mean operation time for vitrectomy was significantly longer in the 27G group than in the 25G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). No statistically significant difference was found between the two groups in terms of the mean operation time for ERM–inner limiting membrane peeling (27G vs 25G: 20.2±9.9 vs 16.1±9.3 min, P=0.14), although the time for vitreous cutting was longer in the 27G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). The flare value, intraocular pressure (IOP), and rate of hypotony 1 day after surgery did not differ between the 27G and 25G groups (flare value: 18.7 vs 17.2; IOP: 8.8 vs 9.7 mm Hg; rate of hypotony: 30 vs 35%, respectively). There was no significant difference in the surgically induced astigmatism between the two groups in the follow-up period. The mean time required for wound closure did not show a significant difference between the 27G and 25G groups (7.7 vs 8.6 weeks, respectively).ConclusionThe 27G system is as safe and useful for ERM vitrectomy as the 25G system. Based on its potential, further improvement of 27G instruments could result in greater efficiency.

Axonal degeneration often leads to the death of neuronal cell bodies. Previous studies demonstrated the crucial role of nicotinamide mononucleotide adenylyltransferase (Nmnat) 1, 2, and 3 in axonal protection. In this study, Nmnat3 immunoreactivity was observed inside axons in the optic nerve. Overexpression of Nmnat3 exerts axonal protection against tumor necrosis factor-induced and intraocular pressure (IOP) elevation-induced optic nerve degeneration. Immunoblot analysis showed that both p62 and microtubule-associated protein light chain 3 (LC3)-II were upregulated in the optic nerve after IOP elevation. Nmnat3 transfection decreased p62 and increased LC3-II in the optic nerve both with and without experimental glaucoma. Electron microscopy showed the existence of autophagic vacuoles in optic nerve axons in the glaucoma, glaucoma+Nmnat3 transfection, and glaucoma+rapamycin groups, although preserved myelin and microtubule structures were noted in the glaucoma+Nmnat3 transfection and glaucoma+rapamycin groups. The axonal-protective effect of Nmnat3 was inhibited by 3-methyladenine, whereas rapamycin exerted axonal protection after IOP elevation. We found that p62 was present in the mitochondria and confirmed substantial colocalization of mitochondrial Nmnat3 and p62 in starved retinal ganglion cell (RGC)-5 cells. Nmnat3 transfection decreased p62 and increased autophagic flux in RGC-5 cells. These results suggest that the axonal-protective effect of Nmnat3 may be involved in autophagy machinery, and that modulation of Nmnat3 and autophagy may lead to potential strategies against degenerative optic nerve disease.

Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG), the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure (IOP) is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer (RNFL) defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy (GON).

PurposeTo determine whether the inverted internal limiting membrane (ILM) flap technique contributes to high reattachment and closure rates in patients with macular hole-associated retinal detachment (MHRD).Patients and methodsIn all, 15 eyes of 15 patients with MHRD undergoing 25-gauge pars plana vitrectomy with the inverted ILM flap technique or ILM peeling. The patients were divided into the inverted ILM flap technique group (6 eyes) and ILM peeling group (9 eyes). The logarithm of minimal angle of resolution best-corrected visual acuity (BCVA) and retinal attachment and macular hole closure rates were compared between the two groups before and after surgery.ResultsNo significant differences were found in the pre- and postoperative BCVA at 1 and 3 months after surgery in either group (inverted ILM flap technique group, preoperatively 1.04±0.55, 1 month 0.95±0.30, 3 months 0.83±0.22; ILM peeling group, preoperatively 1.00±0.44, 1 month 1.05±0.38, 3 months 1.06±0.49; P>0.05, respectively). The postoperative BCVA at 6 months after surgery was significantly better in the inverted ILM flap technique group than in the ILM peeling group (inverted ILM flap technique group, 0.62±0.35; ILM peeling group, 1.02±0.41, P=0.045). The improvement in BCVA was significantly better in the inverted ILM flap technique group than in the ILM peeling group (inverted ILM flap technique group, –0.41±0.29; ILM peeling group, 0.02±0.36; P=0.021). The primary macular hole closure rates were 100% in the inverted ILM flap technique group and 55.5% in the ILM peeling group. The primary reattachment rates were 100% in the inverted ILM flap technique group and 55.5% in the ILM peeling group. The primary macular hole closure and reattachment rates were not significantly different in both groups (P=0.056, respectively).ConclusionThe inverted ILM flap technique is a useful procedure for MHRD in highly myopic eyes.

Autophagy has been shown to be activated in neuronal cells in response to injury and suggested to have a cell-protective role in neurodegenerative diseases. In this study, we investigated the activation of autophagy in retinal ganglion cells (RGCs) following optic nerve transection (ONT) and evaluated its effect on RGC survival. Expression of several autophagy-related genes, including Atg5, Atg7, and Atg12, and autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1 were analyzed at the transcriptional or protein level 1, 3, and 7 days after ONT. Transcription of the Atg5, Atg7, and Atg12 genes was upregulated 1.5-to 1.8-fold in the retina 3 days after ONT compared with that in the controls. Expression of Atg12 mRNA was increased 1.6-fold 1 day after ONT. Seven days after ONT, expression of Atg5, Atg7, and Atg12 mRNA was comparable to that in the untreated retinas. Western blot analysis of proteins isolated from RGCs showed 1.6-, 2.7-, and 1.7-fold increases in LC3-II level 1, 3, and 7 days after ONT, respectively, compared with those in the controls. Expression of beclin-1 was 1.7-fold higher 1 day after RGCs were axotomized, but 3 and 7 days after ONT it was comparable to that of the control. Inhibition of autophagy with bafilomycin A1, 3-methyladenine, and Wortmannin in RGC-5 cells under serum-deprived conditions decreased cell viability by approximately 40%. These results suggest possible activation of autophagy in RGCs after optic nerve transection and demonstrate its protective role in RGC-5 cells maintained under conditions of serum deprivation. V V C 2008 Wiley-Liss, Inc.

Increases of approximately 95% and 75% in RGC survival mediated by alphaA and alphaB overexpression, respectively, were observed 14 days after ONT. At day 7, the RGC protective effect of alphaA and alphaB overexpression was approximately 40%.

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We investigated the neuroprotective effect of thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) which play critical roles in the regulation of oxidative stress on retinal ganglion cells (RGCs) in a rat glaucoma model. Expression of Trx1 and Trx2 and Trx-interacting protein (Txnip) was observed in the RGC layer (GCL), nerve fiber layer and inner nuclear layer. Txnip-, Trx1-and Trx2-expressing cells in the GCL were primarily colocalized with RGCs. The increased Txnip protein level was observed 2 and 5 weeks after glaucoma induction. Trx1 level decreased 2 weeks after glaucoma induction and more prominently after 5 weeks. No change in Trx2 levels was detected. The effects of Trx1 and Trx2 overexpression on RGC survival were evaluated 5 weeks after glaucoma induction. In nontransfected and EGFP-transfected (used as a negative control) retinas, RGC loss was approximately 27% compared with control. The loss of RGCs in Trx1-and Trx2-transfected retinas was approximately 15 and 17%, respectively. Thus, Trx1 and Trx2 preserved 45 and 37% of cells, respectively that were destined to die in glaucomatous retinas. The results of this study provide evidence for the involvement of oxidative stress in RGC degeneration in experimental glaucoma and point to potential strategies to reduce its impact.