Prevalence of ocular hypertension and glaucoma in patients with chronic ocular graft-versus-host disease

Purpose: To compare densities of corneal epithelial dendritic cells (DCs), corneal subbasal nerves, and conjunctival epithelial immune cells (EICs) between patients with dry eye disease (DED) with and without graft-versus-host disease (GVHD) using in vivo confocal microscopy (IVCM). Methods: This study included 54 patients who had moderate to severe DED either associated with (n = 33) or without (n = 21) chronic GVHD. In addition to evaluating clinical parameters of DED, images obtained by laser-scanning IVCM of the central cornea and superior tarsal conjunctiva were analyzed to measure densities of corneal epithelial DCs, corneal subbasal nerves, and conjunctival EICs. Results: Although there were no significant differences between GVHD and non-GVHD groups in symptom scores, the GVHD group had significantly worse corneal fluorescein staining, tear break-up time, and Schirmer's scores than the non-GVHD group. Corneal epithelial DC density, corneal subbasal nerve density, and conjunctival EIC density were 148 ± 135 cells/mm2, 16.3 ± 6.1 mm/mm2, and 670 ± 267 cells/mm2, respectively, in the GVHD group; and 122 ± 99 cells/mm2, 18.3 ± 5.1 mm/mm2, and 572 ± 271 cells/mm2, respectively, in the non-GVHD group. After adjusting for clinical parameters, including the DED severity, none of the IVCM parameters was significantly different between the GVHD versus non-GVHD groups (P = 0.82, P = 0.21, and P = 0.60, respectively). Conclusions: In GVHD-associated DED, cellular changes in the cornea and conjunctiva observed by IVCM were similar to those seen in patients who have non-GVHD dry eye with the same level of disease severity. Therefore, corneal and conjunctival IVCM findings in GVHD-associated DED are possibly reflective of the local disease (DED) severity rather than the underlying systemic disease process

Outcomes of phacoemulsification in patients with chronic ocular graft-versus-host disease

Purpose To evaluate the outcomes of phacoemulsification in patients with ocular graft-versus-host disease (GVHD). Methods The occurrence of cataract, cataract surgery and its outcomes were analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD. Outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and the rate of postoperative complications. Results From 458 eyes evaluated 58 were pseudophakic, from the 400 phakic eyes 238 (59%) presented with cataracts and 62 (26%) underwent cataract surgery. Analysis of postoperative complications and visual outcomes at one month was performed in 51 eyes in which detailed surgical and immediate postoperative records were available. Preoperatively, the mean CDVA was 0.67±0.57 LogMAR (Snellen 20/93) and improved postoperatively to 0.17±0.18 (Snellen 20/29) at one month (P<0.0001), and to 0.13±0.14 (Snellen 20/26) by the final follow-up visit (P<0.0001). Postoperative complications included: corneal epithelial defects (8%), filamentary keratitis (6%), worsening of corneal epitheliopathy (16%), posterior capsular opacification (18%), and cystoid macular edema (4%). A corrected distance visual acuity of 20/30 or better was achieved in 87% of the eyes; suboptimal CDVA improvement was accounted by severe ocular surface disease, pre-existing advanced glaucoma, and prior macular surgery. Conclusions Phacoemulsification in patients with chronic ocular GVHD is a safe and efficacious procedure resulting in significant visual improvement. Overall, postoperative adverse events responded well to timely management

International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I)

The International Chronic Ocular GVHD Consensus Group held 4 working meetings to define new diagnostic metrics for chronic ocular graft-versus-host disease (GVHD). After considering the factors currently used to diagnose chronic ocular GVHD, the Consensus Group identified 4 subjective and objective variables to measure in patients following allogeneic hematopoietic stem cell transplantation (HSCT): OSDI, Schirmer's score without anesthesia, corneal staining, and conjunctival injection. Each variable was scored 0–2 or 0–3, with a maximum composite score of 11. Consideration was also given to the presence or the absence of systemic GVHD. On the basis of their composite score and the presence or absence of systemic GVHD, patients were assigned to one of three diagnostic categories: NO, PROBABLE, or DEFINITE ocular GVHD. New diagnostic criteria for chronic ocular GVHD are presented by the Consensus Group. Validation studies are needed to identify the best combination of the proposed metrics to maximize diagnostic sensitivity and specificity

Safety and Efficacy of the Multitargeted Receptor Kinase Inhibitor Pazopanib in the Treatment of Corneal Neovascularization

Purpose. To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV). Methods. Twenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels. Results. There were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P = 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and <0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up. Conclusions. This preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750)

Wound construction in manual small incision cataract surgery

The basis of manual small incision cataract surgery is the tunnel construction for entry to the anterior chamber. The parameters important for the structural integrity of the tunnel are the self-sealing property of the tunnel, the location of the wound on the sclera with respect to the limbus, and the shape of the wound. Cataract surgery has gone beyond just being a means to get the lens out of the eye. Postoperative astigmatism plays an important role in the evaluation of final outcome of surgery. Astigmatic consideration, hence, forms an integral part of incisional considerations prior to surgery

Onset of Ocular Graft-Versus-Host Disease Symptoms After Allogeneic Hematopoietic Stem Cell Transplantation

Objective To study the factors affecting the time to onset of ocular GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods A retrospective chart review of 200 patients with ocular GVHD was performed to evaluate the association between various donor-recipient characteristics on the time to onset of ocular GVHD after allo-HSCT. Results The median time to onset of chronic ocular GVHD after allo-HSCT was 293 days (range 26 to 2308). Patients receiving fully HLA-matched transplants had a delayed onset of ocular GVHD (median 294 days) compared to mismatched transplants (219 days; P=0.029). HLA-matched transplants from related donors had delayed onset of ocular GVHD (307 days) compared to HLA-matched (286 days; P=0.168) and HLA-mismatched (231 days; P=0.015) transplants from unrelated donors. Ocular GVHD followed systemic GVHD in 76% of patients but preceded systemic disease in 7%, occurred concurrently in 15%, and was not associated with systemic GVHD in 2% of patients. The time elapsed between the occurrence of systemic and ocular GVHD was significantly longer in matched-related transplants (250 days) than in matched-unrelated transplants (120 days; P=0.004). Conclusion The onset of ocular GVHD after allogeneic hematopoietic stem cell transplantation is variable and is influenced by the donor-recipient matching characteristics. In the majority of patients with GVHD ocular involvement follows the occurrence of systemic manifestations; however, importantly, it can also precede or develop independently of systemic disease in a minority. Regular ophthalmic follow-up is recommended after allo-HSCT regardless the concurrent systemic GVHD status

Wound construction in manual small incision cataract surgery

The basis of manual small incision cataract surgery is the tunnel construction for entry to the anterior chamber. The parameters important for the structural integrity of the tunnel are the self-sealing property of the tunnel, the location of the wound on the sclera with respect to the limbus, and the shape of the wound. Cataract surgery has gone beyond just being a means to get the lens out of the eye. Postoperative astigmatism plays an important role in the evaluation of final outcome of surgery. Astigmatic consideration, hence, forms an integral part of incisional considerations prior to surgery

Bilateral corneal ulceration in ocular graft-versus-host disease

Purpose To report on corneal ulceration in ocular graft-versus-host disease (GVHD). Methods This was a retrospective, observational case series investigating corneal ulceration and perforation in a cohort of ocular GVHD patients seen between June 2007 and October 2012. Results Four of 243 ocular GVHD patients developed corneal ulcerations attributable to ocular GVHD, and all four cases involved bilateral corneal ulceration. The median length of time from the diagnosis of ocular GVHD to the diagnosis of the first corneal ulceration was 317 days (range 168–434). The median length of time between the diagnosis of corneal ulceration in each patient’s first and second eye was 248 days (range 9–645). Outcomes varied from complete resolution with medical treatment to corneal perforation necessitating penetrating keratoplasty. In cases of corneal perforation, the median length of time from the diagnosis of corneal ulceration to perforation was 10 days (range 0–20). Common clinical features included: centrally or paracentrally located ulcerations and perforations, concomitant dry eye, and the use of topical or systemic corticosteroids. Conclusion Frequent follow-up and bilateral monitoring are highly recommended in cases of ocular GVHD-associated stromal thinning, as bilateral involvement or rapid progression to corneal perforation can occur

Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial

Purpose: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.Design: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.Participants: Patients aged &gt; 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants &gt;= 2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.Methods: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.Main Outcome Measure: The 52-week endothelial immune rejection rate.Results: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis.Conclusions: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection. (C) 2022 by the American Academy of Ophthalmolog

Bevacizumab in High-Risk Corneal Transplantation

To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.The 52-week endothelial immune rejection rate.Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03–0.65, P = 0.01) in a post hoc Cox regression analysis.In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection