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Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease.

ABSTRACT: PURPOSE:To compare the response of dry eye disease (DED) to treatment with topical steroid in patients with and without graft-vs-host disease (GVHD). DESIGN:Post hoc analysis of a double-masked, randomized clinical trial. METHODS:This single-center study included 42 patients with moderate-to-severe DED associated with (n = 21) or without (n = 21) chronic GVHD. In each group, patients received either loteprednol etabonate 0.5% ophthalmic suspension or artificial tears twice daily for 4 weeks. Clinical data, including Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining (CFS), conjunctival lissamine green staining, tear break-up time (TBUT), and Schirmer test, were evaluated before and after treatment. RESULTS:There were no significant differences in signs and symptoms of DED between the groups at baseline. In non-GVHD patients receiving loteprednol treatment, the average OSDI score decreased by 34% from 49.5 ± 5.9 to 32.6 ± 4.8 (mean ± standard error of the mean, P = .001) and the average CFS score decreased by 41% from 5.6 ± 0.6 to 3.3 ± 0.9 (P = .02). On the other hand, loteprednol treatment in GVHD patients resulted in minimal change in OSDI (59.2 ± 6.7 to 61.1 ± 7.1, 3% increase, P = .66) and CFS (5.5 ± 0.5 to 5.3 ± 1.1, 4% decrease, P = .85) scores. Treatment with artificial tears resulted in 22% decrease of OSDI (P = .10) and 32% decrease of CFS (P = .02) scores in non-GVHD patients, and had minimal effect in patients with GVHD. CONCLUSIONS:DED patients with ocular GVHD have a less favorable response to a low-dose topical steroid regimen compared with those without ocular GVHD even with similar baseline disease severity.

SUBMITTER: Yin J

PROVIDER: S-EPMC8780105 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment.DesignA phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial.ParticipantsPatients with DED secondary to GvHD.MethodsSixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL.Main outcome measuresPrimary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS.ResultsFD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant.ConclusionsFibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

Project description:Despite extensive research in the last few decades, progress in treatment of acute graft-versus-host disease (aGVHD), a common complication of allogeneic hematopoietic cell transplantation (HCT), has been limited and steroids continue to be the standard frontline treatment. Randomized clinical trials (RCTs) have failed to find a beneficial effect of escalating immunosuppression using additional agents. Considering the small number of RCTs, limited sample sizes, and frequent early termination because of anticipated futility, we conducted a systematic review and an aggregate data meta-analysis to explore whether a true efficacy signal has been missed because of the limitations of individual RCTs. Seven reports met our inclusion criteria. The control arm in all studies was 2 mg/kg/day prednisone (or equivalent). The additional agent(s) used in the experimental arm(s) were higher-dose steroids, antithymocyte globulin, infliximab, anti-interleukin-2 receptor antibody (daclizumab and BT563), CD5-specific immunotoxin, and mycophenolate mofetil. Random effects meta-analysis revealed no efficacy signal in pooled response rates at various times points. Overall survival at 100 days was significantly worse in the experimental arm (relative risk [RR], .83; 95% confidence interval [CI], .74 to .94; P = .004, data from 3 studies) and showed a similar trend (albeit not statistically significantly) at 1 year as well (RR, .86; 95% CI, .68 to 1.09; P = .21, data from 5 studies). In conclusion, these results argue against the value of augmented generic immunosuppression beyond steroids for frontline treatment of aGVHD and emphasize the importance of developing alternative strategies. Novel forms of immunomodulation and targeted therapies against non-immune-related pathways may enhance the efficacy of steroids in this setting, and early predictive and prognostic biomarkers can help identify the subgroup of patients who would likely need treatments other than (or in addition to) generic immunosuppression.

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Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease.

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