Person:

Schaumberg, Debra A.

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).

Importance

The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy.

Objective

To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction.

Design and Setting

Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial.

Participants

Seventy-five patients with refractory DED.

Interventions

Participants were randomized to receive treatment with topical anakinra, 2.5% (n=30), anakinra, 5% (n=15), or vehicle (1% carboxymethylcellulose) (n=30) 3 times daily for 12 weeks.

Main Outcomes and Measures

Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye–related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality.

Results

Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P=.12 compared with vehicle and P<.001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P=.88 compared with vehicle and P=.33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P=.11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2of 29 patients (7%) treated with vehicle (P=.03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P=.02 and P=.01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms.

Conclusions and Relevance

Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED.

Purpose

To evaluate the correlation between changes in tear osmolarity, symptoms, and corneal fluorescein staining in patients with dry eye disease (DED). Design

Retrospective, clinic-based cohort study. Methods

In this single-institution study, we reviewed the charts of 186 patients with DED from whom we had data on tear osmolarity, symptoms, and corneal fluorescein staining from two separate visits. Main outcomes included the correlation of the changes between the two visits for tear osmolarity (TearLab® system), symptoms (Ocular Surface Disease Index© [OSDI]), and corneal fluorescein staining (modified Oxford scheme). For tear osmolarity and corneal fluorescein staining the scores from the eye with highest readings were analyzed. The correlations were repeated on subgroups based on proposed cutoffs for DED severity and on patients’ treatment. Results

We found a modest, though statistically significant, correlation between changes in corneal fluorescein staining and symptoms of DED (R = .31; P < .001). However, there was no correlation between the recorded change in tear osmolarity and symptoms (R = −.091; P = .38) or between changes in tear osmolarity and corneal fluorescein staining (R = −.02; P = .80). This lack of correlation was consistent in all the subgroups studied. A multivariate analysis revealed that changes in corneal fluorescein staining had predictive value on symptom changes, while tear osmolarity changes did not. Conclusions

Changes in tear osmolarity do not correlate significantly with changes in patient symptoms or corneal fluorescein staining in dry eye disease.

Purpose

The aim of this study was to compare patient reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI©), a 12-item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency- and severity-based visual analog scale.

Design

Clinic-based evaluation of diagnostic test.

Participants

One hundred fourteen patients with dry eye disease.

Methods

Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate dry eye disease-related symptoms. The correlations between both questionnaires’ scores were evaluated using the Spearman coefficient and their clinical differences were assessed using the Bland-Altman analysis.

Main Outcome Measures

Baseline and follow-up visit OSDI and SANDE dry eye symptom scores.

Results

At the baseline visit, the OSDI and SANDE questionnaire scores significantly correlated (R = 0.64; P <0.001). Moreover, a significant correlation was found between changes in the OSDI and SANDE scores from baseline to follow-up visits (R = 0.47; P <0.001). A Bland-Altman analysis, after score normalization, revealed a difference (bias) of less than two centesimal units between the scores of the two questionnaires.

Conclusions

Data collected from the SANDE questionnaire showed a significant correlation and negligible score differences with those from the OSDI, suggesting that the SANDE visual analog scale-based questionnaire has the potential to provide clinicians with a short, quick and reliable measure for DED symptoms.

Objective

To assess the vision-related quality of life in a cohort of patients with ocular graft-versus-host disease (GVHD).

Design

Prospective study.

Participants

Eighty-four patients diagnosed with chronic ocular GVHD

Methods

We assessed the vision-related quality of life with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires.

Main outcome measures

We assessed vision-related quality of life with NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD to those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and dry eye symptoms measured by OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity, corneal fluorescein staining, tear break-up time, and Schirmer test.

Results

The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5 ± 17. Compared to healthy subjects, ocular GVHD patients reported reduced scores on all NEI-VFQ-25 subscales (each P < 0.001) with exception of color vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = −0.81, P < 0.001), SANDE (R = −0.56, P < 0.001), corneal fluorescein staining (R = −0.36, P = 0.001) and best-corrected visual acuity (R = −0.30, P = 0.004).

Conclusion

Patients with ocular GVHD experience measurable impairment of vision-related quality of life. This study highlights the impact of ocular GVHD on the vision-related quality of life, and hence the importance of comprehensive diagnosis and treatment of this condition.