Ocular surface indicators and biomarkers in chronic ocular graft-versus-host disease: a prospective cohort study.

This longitudinal cohort study compared ocular surface indicators in forty allogeneic hematopoietic stem cell transplant (HSCT) subjects with twenty healthy controls at baseline and identified changes in ocular graft-versus-host disease (oGVHD). Outcome measures included: Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer's test, Oxford corneal staining score, tear break-up time (TBUT), and tear and serum biomarkers (IFN-γ, IL-10, MMP-9, IL-12, IL-13, IL-17α, IL-1ß, IL-2, IL-4, IL-6, IL-8, CXCL10, MCP-1, MIP-1α, RANTES, TNF-α). At baseline the HSCT group had higher median Oxford corneal staining score (1.7 vs. 0.0; P < 0.0001), higher tear TNF-α (20.0 vs. 11.2 pg/mL; P < 0.0001), lower tear RANTES (70.4 vs. 190.2 pg/mL; P < 0.0001), higher serum IL-8 (10.2 vs. 4.5 pg/mL; P = 0.0008), and higher serum TNF-α (8.7 vs. 4.2 pg/mL; P < 0.0001). The incidence of oGVHD was 62% and associated changes included increased Oxford corneal staining score (4.6 vs. 1.8, P = 0.0001), decreased Schirmer's test (3.0 vs. 10.0; P < 0.0001), and decreased TBUT (4.7 vs. 9.0 s; P = 0.0004). Baseline differences in ocular surface indicators suggest a tendency toward ocular dryness in individuals with hematologic disorders preparing for HSCT. Individuals who developed oGVHD showed changes in corneal staining score, Schirmer's test, and TBUT.

One-year pilot study on the effects of nitisinone on melanin in patients with OCA-1B.

BACKGROUND: Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the Tyrosinase gene. METHODS: In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals. RESULTS: The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 ± 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient ≥ 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1], P = 0.04) and left eye (OS, 5 [1.0, 9.1], P = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41], P = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2}, P = 0.01]) and biochemically. CONCLUSION: Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials. CLINICALTRIALS: gov NCT01838655. FUNDING: Intramural program of the National Eye Institute.