Appositional Choroidal Detachment Following XEN45 Gel Stent Requiring Surgical Drainage.

An 82-year-old man with severe primary open-angle glaucoma on maximal medical therapy underwent an ab externo closed conjunctival Xen45 device insertion with mitomycin C. The surgery was uncomplicated, with a first postoperative day intraocular pressure of 4 mm Hg and visual acuity of 20/40 OD. Ten days later, the patient presented with an intraocular pressure of 5 mm Hg and a visual acuity of counting fingers at 5 feet. Examination showed Seidel negative bleb, shallow anterior chamber, and large nonappositional choroidal detachments. Medical therapy with steroids and cycloplegia was initiated. One week later, the serous choroidal detachments became appositional, and Xen explantation and surgical drainage of the choroidal detachment was performed. Postoperatively, the vision improved to 20/60. Significant choroidal detachments can occur after XEN45 implantation requiring surgical intervention.

Acute Macular Neuroretinopathy Following Non-Ocular Trauma: A Hypothesis Regarding Pathophysiologic Mechanism.

BACKGROUND AND OBJECTIVE: To describe the imaging characteristics and clinical course of acute macular neuroretinopathy (AMN) following non-ocular trauma, and to hypothesize a pathophysiologic mechanism for this syndrome. PATIENTS AND METHODS: The records of five patients who developed symptoms and findings suggestive of AMN following trauma to the face or chest were retrospectively reviewed. Optical coherence tomography (OCT), infrared reflectance, fundus autofluorescence, fluorescein and indocyanine green angiography, and multifocal electroretinography were evaluated. RESULTS: Visual symptoms started immediately or very soon after non-ocular trauma, and scotomas persisted at last follow-up (2 weeks to 10 years after trauma). OCT imaging performed within days of the trauma demonstrated focal areas of hyper-reflectivity in the outer plexiform and outer nuclear layers with eventual thinning of the outer nuclear layer, as well as variable loss of the ellipsoid and interdigitation zones. CONCLUSION: Acute ischemic injury caused by trauma-induced hypotension and/or catecholamine release and involving the deep retinal capillary plexus is the pathogenic mechanism that most plausibly explains trauma-associated AMN.

Retinal cell death and current strategies in retinal neuroprotection.

PURPOSE OF REVIEW: Retinal cell death is the main cause of vision loss in many blinding conditions. Research on the basics of how and why retinal cells die in different diseases provides insights into the development of treatment strategies to prevent or reverse this loss. This review summarizes the literature published on this topic in the last year. RECENT FINDINGS: Apoptosis is generally considered the main pathway by which retinal cells die in response to a range of noxious stimuli. However, inhibiting apoptosis does not completely prevent retinal cell death, as many enter programmed necrosis or necroptosis. Many novel ways of inhibiting apoptosis and necrosis, including blockage of the Fas receptor, neuroprotective peptides and antioxidants, continue to be investigated. Also, additional pathways including autophagy and inflammation are being examined on how they contribute to the loss of retinal cells in different disease models. SUMMARY: With more knowledge of how retinal cells die, further advances are being made in prolonging the cell survival. However, even as basic science discoveries remain promising, clinical utility of neuroprotection is still quite limited at this time.

Control of photoreceptor autophagy after retinal detachment: the switch from survival to death.

PURPOSE: To examine whether calpain inhibition following retinal detachment would prolong autophagy and result in reduced photoreceptor apoptosis. METHODS: Retinal detachments were created in Brown-Norway rats by subretinal injection of 1% hyaluronic acid and simulated in vitro by Fas-receptor activation of 661W cells, a cone cell line. Protein levels of LC3 and autophagy-related gene 5 (Atg5), both of which are involved in the creation of the autophagosome, were assayed by Western blot. Calpain 1, the protease responsible for Atg5 cleavage and transitioning photoreceptors from autophagy to apoptosis, activity was monitored by α-spectrin cleavage. Various calpain inhibitors were added either to the subretinal space or cell culture media. Apoptosis was assessed in vitro by caspase-8 activity assays and in vivo via TUNEL assays. Cell counts were assessed in vivo at 2 months following detachment. RESULTS: Following retinal detachment or Fas-receptor activation of 661W cells, there was an increase in Atg5 and LC3-II that peaked at 3 days and decreased by 7-days postdetachment. Calpain 1 activity level peaked at 7 days and was associated with decreased autophagy. Calpain inhibition led to increased autophagy, a decrease in caspase-8 activation, reduced TUNEL-positive photoreceptors, and increased photoreceptor cell survival. CONCLUSIONS: Our data suggest that calpain activation, which peaks at 7-days postdetachment, is a key step in triggering photoreceptors to shift from cell survival to death. Prolonging autophagy through calpain inhibition leads to significantly reduced photoreceptor apoptosis and increased cell survival.

Treatment of subretinal fluid associated with dome-shaped macula.

Dome-shaped macula is a recently described disorder seen in eyes with myopic posterior staphyloma. Vision loss may accompany sub-macular fluid accumulation, for which no effective treatment has been reported. The authors report the successful treatment of two female patients, aged 34 and 59 years, with chronic exudative macular detachment associated with dome-shaped macula. Symptoms of subretinal fluid had been present for at least 2 years in each case, and the fluid was refractory to multiple intravitreal bevacizumab injections in one eye. After a single session of half-fluence verteporfin photodynamic therapy, the submacular fluid resolved completely in each eye. In one eye, recurrent submacular fluid 2 years later responded partially to repeat photodynamic therapy and completely to focal laser photocoagulation. [Ophthalmic Surg Lasers Imaging Retina. 2013;44:593-595.].

Autophagy activation in the injured photoreceptor inhibits fas-mediated apoptosis.

PURPOSE: To examine the activation of autophagy and its relationship to Fas-mediated photoreceptor apoptosis during experimental retinal detachment. METHODS: Retina-retinal pigment epithelium (RPE) separation was created in Brown-Norway rats by subretinal injection of 1% hyaluronic acid and the intraretinal levels of the autophagy proteins LC3 and Atg5, the time course of LC3-I to LC3-II conversion, and the activation of cathepsins B and D were assayed with Western blot analysis and immunohistochemistry. We measured the ability of a Fas-activating antibody to induce LC3-I to LC3-II conversion in 661W cells, and the in vivo effect of Met12, a small molecule inhibitor of the Fas receptor, on LC3-I to LC3-II conversion and Atg5 expression. Autophagy activation was inhibited using 3-methyladenine (3-MA) or siRNA knockdown of Atg5 and the effect on apoptosis was measured using a caspase 8 activity assay, caspase 8 immunoblots, and photoreceptor TUNEL staining. RESULTS: Retina-RPE separation resulted in a Fas-dependent activation of autophagy, with increased Atg5 levels and intraphotoreceptor conversion of LC3-I to LC3-II. Detached retinas had increased levels of autophagosome-associated lysosomal proteases, cathepsins B and D. Inhibition of autophagy by 3-MA or siAtg5 accelerated the time course of caspase 8 activation and photoreceptor TUNEL staining. CONCLUSIONS: Autophagy activation occurs in the photoreceptors after retina-RPE separation. This appears to be, at least in part, dependent on Fas receptor activation, and plays a role in regulating the level of photoreceptor apoptosis.

Inhibition of retinal detachment-induced apoptosis in photoreceptors by a small peptide inhibitor of the fas receptor.

Purpose. To test the effect of a small peptide inhibitor (Met12) of the Fas receptor on the activation of extrinsic and intrinsic apoptosis pathways after retinal detachment. Methods. Retinal-RPE separation was created in Brown Norway rats by subretinal injection of 1% hyaluronic acid. Met12, derived from the Fas-binding extracellular domain of the oncoprotein Met, was injected into the subretinal space at the time of separation. A mutant peptide and vehicle administered in a similar fashion acted as inactive controls. The extrinsic apoptotic pathway was induced in 661W cells using a Fas-activating antibody in the presence or absence of Met12. Caspase 3, caspase 8, and caspase 9 activities were measured with calorimetric and luminescent assays in retinal extracts and cell lysates. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed in retinal sections 3 days after separation. Histology was performed in retinal sections 2 months after retinal detachment. Results. Met12 inhibited Fas-induced caspase 8 activation in 661W cells. Similarly, administration of Met12 into the subretinal space inhibited the activation of caspase 3, caspase 8, and caspase 9 after retinal detachment. This corresponded to a decreased level of TUNEL-positive staining of photoreceptors after retinal-RPE separation in animals that received Met12, but not inactive mutant, peptide treatment. After 2 months, the outer nuclear layer was significantly thicker, and the photoreceptor count was higher in animals treated with subretinal Met12. Conclusions. The small peptide Met12 may serve as a photoreceptor-protective agent in the setting of retinal-RPE separation.