Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study.

Purpose: To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed. Results: Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms. Conclusion: oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.

Outcomes of Ahmed glaucoma valve and transscleral cyclophotocoagulation in neovascular glaucoma.

Purpose: To determine the outcomes of Ahmed glaucoma valve (AGV) and transscleral diode cyclophotocoagulation (CPC) in neovascular glaucoma (NVG). Methods: This was a single-center retrospective comparative case series involving chart review of consecutive patients who underwent AGV or CPC for treatment of NVG and had ≥6 months of follow-up. Surgical failure at 6 months, defined as an IOP of >21 or <6 mm Hg with hypotony maculopathy after 1 month, progression to no light perception (NLP) vision, glaucoma reoperation, or removal of AGV were the main outcome measures. Results: In total, 121 eyes of 121 patients were included (70 AGV and 51 CPC). Baseline demographics, visual acuity (VA), and intraocular pressure (IOP) were comparable between groups. At 6 months, failure was significantly higher in the CPC group than in the AGV group (43.1% vs. 17.1%, P = 0.020). Both groups had similar IOP and medication number at 6 months, but VA was significantly lower in the CPC group compared to the AGV group (2.4 ± 0.8 vs. 1.9 ± 1.0, P = 0.017). More CPC eyes required reoperation for glaucoma than AGV eyes (11.8% vs. 1.4%, P = 0.041). Multivariate regression analysis identified higher preoperative IOP (P = 0.001) and CPC surgery (P = 0.004) as independent predictors of surgical failure at 6 months. Age, sex, race, NVG etiology, bilaterality of the underlying retinal pathology, perioperative retina treatment, and prior or combined vitrectomy were not significant. Conclusion: AGV and CPC had comparable IOP and medication reduction in NVG eyes at 6 months. CPC was more frequently associated with failure, reoperation for glaucoma, and worse visual outcomes. High preoperative IOP and CPC surgery independently predicted surgical failure.

Effect of shunt type on rates of tube-cornea touch and corneal decompensation after tube shunt surgery in uveitic glaucoma.

PURPOSE: To evaluate the effect of tube shunt type [Ahmed (AGV) versus Baerveldt (BGI)] on the frequency of tube-cornea touch and corneal decompensation after tube shunt surgery. METHODS: This retrospective comparative study included 145 eyes of 130 patients with uveitic glaucoma who underwent AGV (75 eyes) or BGI (70 eyes) implantations. Electronic medical records were reviewed to document demographic factors, intraocular pressure (IOP) reduction, frequency of tube-cornea touch, corneal decompensation, and need for subsequent corneal transplantation. RESULTS: The mean follow-up was 27.7±3.3 months for AGV and 32.8±3.8 months for BGI (p=0.30). Tube-cornea touch was observed in 5 eyes after BGI and 1 eye in the AGV group (p=0.08). The BGI group reported a significantly higher rate of corneal decompensation (9 versus 0; p=0.001) and transplantation (6 versus 0; p=0.01) compared to the AGV group. Previous trabeculectomy was a significant risk factor for corneal complications in eyes undergoing BGI implantation (odds ratio [OR]= 8.17, 95% confidence interval [CI]=1.78-37.45, p=0.007). CONCLUSION: Similar rates of tube-cornea touch were observed in both shunt types; BGI shunts were associated with a greater incidence of corneal complications and transplantation as compared to AGV in this retrospective series of uveitic glaucoma cases.

Ahmed Versus Baerveldt Glaucoma Drainage Device in Uveitic Glaucoma: A Retrospective Comparative Study.

PRECIS: Baerveldt glaucoma drainage device demonstrated a greater reduction in intraocular pressure (IOP) than Ahmed in patients with uveitic glaucoma. The most common cause of failure was uncontrolled IOP in Ahmed and hypotony in the Baerveldt group. PURPOSE: To compare the efficacy and safety of Ahmed and Baerveldt glaucoma drainage devices in uveitic glaucoma. MATERIALS AND METHODS: The retrospective comparative study included patients with uveitic glaucoma who underwent Ahmed or Baerveldt glaucoma drainage device implantation with a minimum follow-up of 3 months. Success was defined as IOP ≥6 and ≤21 mm Hg and >20% reduction on 2 consecutive visits after the third month with (qualified success) or without (complete success) medications and no further glaucoma surgery or loss of vision. IOP, number of medications, visual acuity, complications, and interventions were compared between groups. RESULTS: In total, 137 eyes of 122 patients (67 Ahmed, 70 Baerveldt) were included. The preoperative IOP and number of medications in the Ahmed group (32.7±10.3 mm Hg; 4.1±1.3) were similar to Baerveldt (32.1±10.2 mm Hg; 4.3±1.3; P=0.73, 0.35). These at the last follow-up were (18.1±9.8 mm Hg; 2.1±1) in Ahmed and (12.7±6.9 mm Hg; 1.3±1.3) in Baerveldt groups (P=0.04, 0.01). The Baerveldt had greater IOP reduction (60.3% vs. 44.5%) and complete success rate (30% vs. 9%) with higher complication rate (51.4% vs. 20.9%) (all P≤0.05). The de novo glaucoma reoperation rate was 19% in the Ahmed group and 4% in the Baerveldt group (P=0.006). Hypotony resulted in failure in 7 eyes (10%) in the Baerveldt group and none in the Ahmed group (P=0.013). CONCLUSIONS: Higher complete success rate and significantly greater reduction in mean IOP and number of medications were observed in the Baerveldt group, but with a higher rate of complications including hypotony.

Crystal Structure of Recoverin with Calcium Ions Bound to Both Functional EF Hands.

Recoverin (Rv), a small Ca(2+)-binding protein that inhibits rhodopsin kinase (RK), has four EF hands, two of which are functional (EF2 and EF3). Activation requires Ca(2+) in both EF hands, but crystal structures have never been observed with Ca(2+) ions in both sites; all previous structures have Ca(2+) bound to only EF3. We suspected that this was due to an intermolecular crystal contact between T80 and a surface glutamate (E153) that precluded coordination of a Ca(2+) ion in EF2. We constructed the E153A mutant, determined its X-ray crystal structure to 1.2 Å resolution, and showed that two Ca(2+) ions are bound, one in EF3 and one in EF2. Additionally, several other residues are shown to adopt conformations in the 2Ca(2+) structure not seen previously and not seen in a second structure of the E153A mutant containing Na(+) instead of Ca(2+) in the EF2 site. The side-chain rearrangements in these residues form a 28 Å allosteric cascade along the surface of the protein connecting the Ca(2+)-binding site of EF2 with the active-site pocket responsible for binding RK.