Glaucoma management after corneal transplantation surgeries

Purpose of reviewIntraocular pressure (IOP) elevation and glaucoma progression following corneal transplantation, specifically, penetrating keratoplasty, Descemet's stripping endothelial keratoplasty, and Boston keratoprosthesis, are well described causes of ocular morbidity. Depending on the procedure performed, the incidence of glaucoma is highly variable. Several etiologic factors have been identified, the most common being synechial angle closure and corticosteroid-induced IOP elevation. The purpose of this review is to describe the various treatment strategies for glaucoma following corneal transplantation.Recent findingsMedications and laser treatments are usually first-line therapies for postoperative IOP elevation. Surgical intervention, including filtering surgery and glaucoma drainage devices, may be necessary to control IOP and prevent progressive glaucomatous damage.SummaryGlaucoma is a common complication of corneal transplantation, and the degree of aggressiveness is often related to the indication for corneal surgery. Although postoperative IOP elevation may be controlled with medical therapy alone, refractory cases may require glaucoma surgery. In all cases, early detection and intervention are necessary to optimize patient outcomes

Evaluation of the "IS" Rule to Differentiate Glaucomatous Eyes From Normal

To compare the accuracy of the "ISNT" rule [neural rim width of inferior(I)≥superior(S)≥nasal(N)≥temporal(T) regions] and the abbreviated variant, the "IS" rule (inferior≥superior regions) to differentiate normal from glaucomatous eyes. Medical records of patients who were evaluated in 2011, had glaucomatous optic neuropathy and visual field defects, on glaucoma treatment, and had stereoscopic optic disc photographs were reviewed. Optic discs with focal complete loss of neural rim or long axis rotated >30 degrees from vertical meridian, and patients with ≥5 D of myopia or any retinal pathology or nonglaucomatous optic neuropathy were excluded. One eye per patient was randomly enrolled. Normal control eyes were also included. Rim widths were measured with an image processing program (ImageJ, National Institutes of Health) in a masked manner. The sensitivity and specificity of the ISNT rule, the IS rule, and cup-to-disc ratio (CDR) were compared. A total of 134 glaucoma and 110 normal eyes were enrolled. The mean CDRs of the glaucoma and normal eyes were 0.65±0.13 and 0.39±0.15, respectively. Sensitivities of the ISNT and IS rules were 85% and 41%, respectively, whereas specificities were 46% and 85%, respectively. Application of the IS rule in eyes with larger CDR (>0.57) increased the specificity of the IS rule to 93% while keeping the sensitivity at 41%. When ISNT or IS rule and CDR>0.57 were combined in differentiating normal from glaucomatous eyes for the entire sample, specificities approached 90% and 99%, respectively. The ISNT rule alone has a high sensitivity but relatively low specificity. Application of the IS rule in eyes with increased CDR yields a much higher specificity for differentiating normal from more advanced glaucomatous eyes. A combination of different features of the optic disc (increase of CDR and ISNT or IS rule) improves the specificity of optic disc evaluation for glaucoma

Vesicular Release of GABA by Mammalian Horizontal Cells Mediates Inhibitory Output to Photoreceptors

Feedback inhibition by horizontal cells regulates rod and cone photoreceptor calcium channels that control their release of the neurotransmitter glutamate. This inhibition contributes to synaptic gain control and the formation of the center-surround antagonistic receptive fields passed on to all downstream neurons, which is important for contrast sensitivity and color opponency in vision. In contrast to the plasmalemmal GABA transporter found in non-mammalian horizontal cells, there is evidence that the mechanism by which mammalian horizontal cells inhibit photoreceptors involves the vesicular release of the inhibitory neurotransmitter GABA. Historically, inconsistent findings of GABA and its biosynthetic enzyme, L-glutamate decarboxylase (GAD) in horizontal cells, and the apparent lack of surround response block by GABAergic agents diminished support for GABA's role in feedback inhibition. However, the immunolocalization of the vesicular GABA transporter (VGAT) in the dendritic and axonal endings of horizontal cells that innervate photoreceptor terminals suggested GABA was released via vesicular exocytosis. To test the idea that GABA is released from vesicles, we localized GABA and GAD, multiple SNARE complex proteins, synaptic vesicle proteins, and Cav channels that mediate exocytosis to horizontal cell dendritic tips and axonal terminals. To address the perceived relative paucity of synaptic vesicles in horizontal cell endings, we used conical electron tomography on mouse and guinea pig retinas that revealed small, clear-core vesicles, along with a few clathrin-coated vesicles and endosomes in horizontal cell processes within photoreceptor terminals. Some small-diameter vesicles were adjacent to the plasma membrane and plasma membrane specializations. To assess vesicular release, a functional assay involving incubation of retinal slices in luminal VGAT-C antibodies demonstrated vesicles fused with the membrane in a depolarization- and calcium-dependent manner, and these labeled vesicles can fuse multiple times. Finally, targeted elimination of VGAT in horizontal cells resulted in a loss of tonic, autaptic GABA currents, and of inhibitory feedback modulation of the cone photoreceptor Cai, consistent with the elimination of GABA release from horizontal cell endings. These results in mammalian retina identify the central role of vesicular release of GABA from horizontal cells in the feedback inhibition of photoreceptors

Early Aqueous Suppressant Therapy on Hypertensive Phase Following Glaucoma Drainage Device Procedure: A Randomized Prospective Trial

To prospectively evaluate the effect of early aqueous suppression (therapy) on hypertensive phase (HP) and intraocular pressure (IOP) control after implantation of silicone Ahmed glaucoma valve (AGV). Patients who underwent AGV implantation were randomized to initiate therapy (including β-blockers, α-agonists, or carbonic anhydrase inhibitors) when postoperative IOP>10 mm Hg (low-IOP initiation group) or >17 mm Hg (moderate-IOP initiation group). HP was defined as an IOP>21 mm Hg during the first 6 postoperative months, after an initial IOP reduction to <22 mm Hg in the first postoperative week. Primary outcome measures included the occurrence of HP and IOP control. Fifty-two eyes (50 patients) underwent AGV implantation. Average follow-up was 21.9±10.7 months. HP was observed in 21 eyes (40.4%) with average peak IOP of 30±8 mm Hg, onset at 32±30 days, and duration of 15±32 days. One year postoperatively, those eyes with HP had higher IOP than eyes that did not develop HP (15.1±5.2, 11.4±4.3, respectively; P=0.021) and required more additional glaucoma surgeries (28.6%, 3.2%, respectively; P=0.013). The peak IOP at week 3 postoperatively in the low-IOP initiation group (26 eyes) was significantly lower than in the moderate-IOP initiation group (26 eyes; 15.7±3.6, 20.6±8.9, respectively; P=0.012). Eyes with therapy started after HP onset had significantly higher postoperative IOP from 2 to 4 months. Therapy initiated before the development of HP was not associated with a higher complication rate. Aqueous suppression initiated in the early postoperative period while IOPs were still in the low-teens and was able to reduce the incidence of IOP spike associated with the HP without an increased complication rate

Visual Field Outcomes in the Tube Versus Trabeculectomy Study

To describe visual field (VF) outcomes in the Tube Versus Trabeculectomy (TVT) Study. Cohort analysis of patients in a multicenter randomized clinical trial. A total of 122 eyes of 122 patients, with 61 eyes in both the tube shunt and trabeculectomy groups. The TVT Study is a multicenter randomized clinical trial comparing the safety and efficacy of tube shunt surgery (350-mm Baerveldt implant) and trabeculectomy with mitomycin C (MMC) (0.4 mg/ml for 4 minutes) in patients with previous cataract or glaucoma surgery. Enrolled patients underwent perimetry at baseline and annual follow-up visits. The VFs were included if the false-positive rate was ≤20% and false-negative rate was ≤35%. The VFs were excluded if visual acuity <20/400 or loss of ≥2 Snellen lines from baseline was attributed to an etiology other than glaucoma. Longitudinal linear mixed-effects models with best linear unbiased predictions (BLUPs) were applied to estimate rates of change in mean deviation (MD) for each treatment group. Rate of MD change during follow-up period. A total of 436 reliable VFs were analyzed, with an average of 3.6 VFs per eye. Baseline MD was -13.07 ± 8.4 decibels (dB) in the tube shunt group and -13.18 ± 8.2 dB in the trabeculectomy group (P = 0.99). The rate of change in MD was -0.60 dB/year in the tube group and -0.38 dB/year in the trabeculectomy group (P = 0.34). The 95% confidence intervals for the rates of MD change were -0.77 to -0.44 dB/year in the tube group and -0.56 to -0.20 dB/year in the trabeculectomy group. No significant difference in MD slope was seen when patients were categorized by percentage of visits with intraocular pressure (IOP) <18 mmHg or by average IOP. Univariable and multivariable risk factor analyses identified history of diabetes, elevated IOP, and worse MD as baseline factors associated with more rapid VF loss. Slow rates of VF loss were observed after randomized surgical treatment in the TVT Study, but no significant difference in the rate of VF loss was seen after tube shunt implantation and trabeculectomy with MMC. Patients with diabetes, higher IOP, and more severe VF loss at baseline were at higher risk for VF progression

Gold Shunt in the treatment of refractory glaucoma

When medical therapy fails to control intraocular pressure, the standard surgical approaches for treating glaucoma are trabeculectomy and aqueous shunt implantation. However, alternative surgical techniques and devices are being investigated in an effort to avoid the potentially serious complications associated with filtering procedures. In patients who have previously undergone incisional glaucoma surgery, surgical options may be particularly limited because of conjunctival scarring. One novel device that has gained significant interest is the Gold Shunt, a non-valved flat-plate drainage implant that diverts aqueous humor from the anterior chamber into the suprachoroidal space. Ideally, this 'blebless' procedure is less prone to the postoperative complications that can lead to failure in standard glaucoma surgeries and does not rely on conjunctival manipulation or integrity to form a bleb. This device profile reviews the current literature and evidence for Gold Shunt implantation in refractory glaucoma