Hasanain Shikari

Ocular Graft-versus-Host Disease: A Review

Graft-versus-host disease (GVHD) is a common cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic findings involving the skin, gastrointestinal tract, and liver often overshadow the other manifestations of GVHD. Ocular surface disease remains the most common cause of long-term morbidity in GVHD. Herein, the etiology, pathophysiology, clinical manifestations, and treatment of acute and chronic systemic GVHD are reviewed, with a focus on ocular GVHD.

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, Schirmers 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.

Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years

OBJECTIVE To determine whether peripheral diabetic retinopathy (DR) lesions identified on ultrawide field (UWF) imaging are associated with increased DR progression. DESIGN Prospective, longitudinal cohort. PARTICIPANTS Two hundred eyes of 100 participants previously enrolled in a comparative instrument validation study. METHODS Baseline mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and UWF images were obtained. On UWF images, DR lesions with a greater extent outside versus inside standard ETDRS fields were defined as predominantly peripheral lesions (PPLs). Follow-up ETDRS photographs were obtained 4.2±0.3 years after baseline. Baseline and follow-up DR severity were graded from ETDRS photographs. MAIN OUTCOME MEASURES Rates of 2-step or more progression and progression to proliferative DR (PDR) in eyes with PPLs compared with eyes without PPLs identified on UWF imaging at baseline. RESULTS In eyes without PDR (n = 109) at baseline, 56 (51%) had at least 1 field with PPLs and 43 (39%) had DR progression. Compared with eyes without PPLs, eyes with PPLs had a 3.2-fold increased risk of 2-step or more DR progression (6 [11%] vs. 19 [34%]; P = 0.005) and a 4.7-fold increased risk for progression to PDR (3 [6%] vs. 14 [25%]; P = 0.005). These findings remained statistically significant after adjusting for gender, diabetes type, diabetes duration, hemoglobin A1c (HbA1c) levels, and baseline DR severity. Increasing extent of fields with PPLs increased the risk for 2-step or more DR progression (P = 0.004) and progression to PDR (P = 0.009). CONCLUSIONS Presence and increasing extent of PPLs were associated with increased risk of DR progression over 4 years, independent of baseline DR severity and HbA1c levels. Increasing extent of PPLs substantially increased the risk of DR progression and progression to PDR, especially with less severe DR at baseline. These findings demonstrate that detailed peripheral retinal evaluation provides important information that is necessary to assess completely the risk of DR progression.

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).

Complications of Intravitreal Injections in Patients with Diabetes

Abstract Intravitreal injections for the treatment of retinal disorders and intraocular infection have become a common ophthalmic procedure, and injections of anti-vascular endothelial growth factor agents or steroids are frequently performed for the treatment of diabetic macular edema or other diabetic vascular pathology. Diabetic patients may be at higher risk of adverse events than non-diabetic individuals given frequent systemic co-morbidities, such as cardiovascular and renal disease, susceptibility to infection, and unique ocular pathology that includes fibrovascular proliferation. Fortunately, many associated complications, including endophthalmitis, are related to the injection procedure and can therefore be circumvented by careful attention to injection techniques. This review highlights the safety profile of intravitreal injections in patients with diabetes. Although diabetic patients may theoretically be at higher risk than non-diabetic patients for complications, a comprehensive review of the literature does not demonstrate substantial increased risk of intravitreal injections in patients with diabetes.

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.

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 graft-versus-host disease (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 and 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, 26–2308 days). Patients receiving fully human leukocyte antigen (HLA)–matched transplants had a delayed onset of ocular GVHD (median, 294 days) compared with mismatched transplants (219 days; P = 0.029). HLA-matched transplants from related donors had delayed onset of ocular GVHD (307 days) compared with 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). Conclusions: The onset of ocular GVHD after allo-HSCT is variable and is influenced by 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 of patients. Regular ophthalmic follow-up is recommended after allo-HSCT regardless of concurrent systemic GVHD status.

Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD

PURPOSE To evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD. METHODS Retrospective review and data modeling. We reviewed the records of post-bone marrow transplantation patients who were newly diagnosed with ocular GVHD and initiated therapy, and analyzed changes in symptoms (Ocular Surface Disease Index [OSDI]; Symptom Assessment in Dry Eye [SANDE]) and signs (corneal fluorescein staining [CFS]; Schirmer test). We used a LOESS technique to fit a model in function of data variations and obtain a predictive value of the scores progression over time. RESULTS The records of 123 patients who were followed-up for over 2 years (up to 62 months) were reviewed. The median baseline scores recorded were: OSDI 52 units, SANDE 62.2 units, CFS 2.0 Oxford units, and Schirmer 4 mm. After six months of follow up, scores improved for OSDI (-18.6 units, p = 0.007), SANDE (23.7 units, p = 0.01), and CFS (-0.7 Oxford units, p < 0.001). Data analysis showed that after a 2-year follow up the three parameters continued to improve: OSDI -13.67 units (27% reduction), SANDE -17.55 units (28%), CFS -1.1 units (54%), but Schirmer test scores progressively worsened -1.2 mm (22%). CONCLUSION In patients with ocular GVHD symptoms and corneal fluorescein staining improved after initiation of treatment, meanwhile Schirmer scores declined progressively. This indicates that appropriate treatment in chronic ocular GVHD can lead to mid- and long-term improvements in symptoms and corneal epitheliopathy; however, sustained reduction in Schirmer test scores suggests chronic tear production impairment.