Myeloid differentiation factor 88 expression in eyelid specimens of rosacea.

PURPOSE: Rosacea is a common cause of ocular surface disease. Specific immunologic features have been implicated in its pathogenesis, including toll-like receptors, mitogen-associated kinase, and nuclear factor kappa-B. Myeolid differentiation factor 88 (MYD88) has been associated with these elements, suggesting a role for this protein in rosacea. This study was designed to compare the expression of MYD88 in the eyelids of patients with and without this disease. METHODS: Western blotting for MYD88 was performed in 14 control patients and 15 patients with rosacea. Bands were quantified and normalized to actin. Immunohistochemical staining for MYD88 was performed in a different cohort of 12 patients with rosacea and 12 controls, and positively-staining cells were counted across five consecutive 40x fields. Statistical analyses compared the differences between the two groups via a dedicated software package. RESULTS: On western blotting, the mean ratios of MYD88 to actin were 13.8 (standard deviation = 14.1) and 44.3 (standard deviation = 39.6) in control and rosacea patients, respectively (p = .002). On immunohistochemistry, the mean numbers of positively-staining cells were 12.1/40x field (standard deviation = 9.61/40x field) and 27.4/40x (standard deviation = 18.7/40x field) in control and rosacea patients, respectively (p = .0438). CONCLUSIONS: MYD88 is enriched in eyelid specimens of rosacea. This finding further implicates the innate immune system in the pathogenesis of rosacea, and is consistent with previous reports regarding the role of this protein in ocular surface disease and the previously-implicated cellular features of the disease. Inhibition of MYD88 may be a successful treatment strategy to manage rosacea.

Retinal Detachment after Treatment of Retinopathy of Prematurity with Laser versus Intravitreal Anti-Vascular Endothelial Growth Factor.

PURPOSE: To compare rates of short-term retinal detachment (RD) of infants treated for type 1 retinopathy of prematurity (ROP) with intravitreal anti-vascular endothelial growth factor (VEGF) therapy with infants treated with laser therapy. The choice between these 2 treatments remains controversial. Comparative data are limited and describe re-treatment rates rather than retinal structural outcomes predictive of long-term vision. Anti-vascular endothelial growth factor acts faster than laser therapy, which may be beneficial for more aggressive ROP. DESIGN: Nonrandomized, comparative cohort study. PARTICIPANTS: The study included 1167 eyes of 640 infants treated for type 1 ROP. Among these, 164 eyes received anti-VEGF therapy and 1003 eyes received laser therapy. METHODS: Pretreatment and posttreatment examinations and treatments were completed by ophthalmologists with expertise in ROP. The study was a secondary analysis of data from the retrospective Postnatal Growth and Retinopathy of Prematurity Study (G-ROP) 1 study (2006-2012) and the prospective G-ROP 2 study (2015-2017). MAIN OUTCOME MEASURES: Rate of RD (ROP stages 4A, 4B, or 5) within 8 weeks of initial treatment, an end point predictive of poor long-term vision. The results were stratified by postmenstrual age (PMA) at treatment as occurring before versus at or after 36 weeks and 0 days, because earlier disease may be considered more aggressive. RESULTS: Among 458 eyes treated before PMA 36 weeks and 0 days, the short-term RD rate was higher after laser therapy (29/368 eyes [7.9%]) than after anti-VEGF therapy (0/90 eyes [0%]; P < 0.001). Of 709 eyes treated at or after PMA 36 weeks and 0 days, short-term RD risk did not differ between groups (laser [20/635 eyes], 3.1%; anti-VEGF [1/74 eyes], 1.4%; P = 0.27). CONCLUSIONS: Anti-vascular endothelial growth factor therapy results in better short-term structural outcomes than laser therapy when type 1 ROP is treated before 36 weeks' PMA. After this age, both treatments have very low rates of short-term RD. The faster action of anti-VEGF agents likely is responsible for these findings.

Cytotoxic T-Lymphocyte-Associated Protein-4 and Lymphocyte Activation Gene-3 Expression in Orbitally-Invasive Versus Nodular Basal Cell Carcinoma.

PURPOSE: To compare the expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in nodular and orbitally-invasive forms of basal cell carcinoma (BCC). METHODS: Immunohistochemical staining for CTLA-4 and LAG-3 was performed on the pathology specimens of BCC from orbital exenteration and nodular forms. The numbers of positively-staining cells/×40 field were counted across 5 consecutive fields of each specimen and statistical analysis was performed to calculate the difference in expression between the 2 groups. RESULTS: Nine cases of orbitally-invasive BCC and 6 cases of nodular BCC were studied. The mean numbers of CTLA-4-positively staining cells were 11.51 cells/×40 field (median = 6.60 cells/×40 field, range = 0.4-31.8 cells/×40 field) in invasive BCC and 0.90 cells/×40 field (median = 0.60 cells/×40 field, range = 0.0-2.8 cells/×40 field) in nodular specimens. The difference between the 2 groups was statistically significant (p = 0.0030). The mean number of LAG-3-positively staining cells was 0.58 cells/×40 field (median = 0.0, range = 0.0-2.8 cells/×40 field) in invasive BCC and 3.13 cells/×40 field (median = 0.0, range = 0.0-18.18 cells/×40 field). There was no significant difference in LAG-3 positivity between tumor groups (p = 0.5564). CONCLUSIONS: CTLA-4 expression was enriched in orbitally invasive BCC compared with nodular forms of BCC, whereas LAG-3 expression did not differ between these entities. CTLA-4 mediated immune suppression may facilitate the development of orbitally invasive BCC. Treatment strategies that use existing medications to target CTLA-4 may decrease the requirement for orbital exenteration and provide enhanced survival outcomes.

A comparison of primary laser versus laser after anti-vascular endothelial growth factor for type 1 retinopathy of prematurity.

PURPOSE: To compare characteristics of laser treatment for high-risk type 1 retinopathy of prematurity (ROP) in eyes treated with primary laser versus laser after an initial treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: The medical records of consecutive patients at a single academic institution treated for type 1 ROP before 36 weeks' postmenstrual age with primary laser versus laser after initial treatment with anti-VEGF were reviewed retrospectively. Outcome measures were laser spot number, mean laser power, total laser energy (Joules), and retinal vascularization to the nasal ora at time of laser treatment. RESULTS: Compared with the 46 eyes treated with primary laser, the 46 eyes treated with laser after anti-VEGF required fewer spots (mean, 775 vs 1418 [P < 0.01]), less power (182 vs 223 mW [P < 0.01]), and less total energy (27 vs 61 Joules [P < 0.01]), and showed greater vascularization to the nasal ora at the time of laser treatment (47.8% vs 6.5% [P < 0.01]). CONCLUSIONS: In our study cohort, laser after initial anti-VEGF treatment may have allowed for greater retinal vascularization and been less destructive than primary laser for high-risk type 1 ROP.

A Comparison of Respiratory Outcomes after Treating Retinopathy of Prematurity with Laser Photocoagulation or Intravitreal Bevacizumab.

PURPOSE: To compare respiratory outcomes after treatment of retinopathy of prematurity (ROP) between infants treated with laser therapy under general anesthesia and infants treated with intravitreal bevacizumab under bedside sedation. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred thirty-eight consecutive infants treated for ROP from September 2010 through September 2018 at 1 institution. METHODS: Retrospective medical, procedural, and ophthalmologic data were collected, including preprocedure (baseline) and postprocedure (24 hours, 48 hours, 7 days, and 28 days) respiratory status, birth weight, gestational age, gender, ROP treatment method, postmenstrual age at treatment, and coincident nonocular procedures during anesthesia. Respiratory outcomes at 48 hours were compared between infants treated with laser therapy under general anesthesia and infants treated with intravitreal bevacizumab under local sedation using multivariate logistic regression analysis to control for potentially confounding factors. MAIN OUTCOME MEASURES: Proportion of infants who had returned to their respiratory baseline by 48 hours after ROP treatment. RESULTS: Return to respiratory baseline was significantly less common among 119 infants initially treated with laser therapy compared with 19 infants initially treated with bevacizumab at 24 hours (40% vs. 74%; P = 0.0115), 48 hours (53% vs. 79%; P = 0.0453), and 7 days (79% vs. 100%; P = 0.0242). In a multivariate logistic regression analysis, infants treated with laser therapy were less likely to return to respiratory baseline at 48 hours (odds ratio, 0.14; 95% confidence interval, 0.04-0.54). At 28 days, no difference was found between groups (laser, 97%; bevacizumab, 100%; P > 0.99). CONCLUSIONS: Infants treated with intravitreal bevacizumab using bedside sedation returned to their preprocedure respiratory baseline faster than infants treated with laser under general anesthesia, with the differences persisting at least to 7 days or more after the procedure.