Topical netarsudil for treatment of glaucoma with elevated episcleral venous pressure: A pilot investigation in sturge-weber syndrome.

PURPOSE: Topical netarsudil 0.02% may reduce intraocular pressure (IOP) by decreasing episcleral venous pressure (EVP), which carries theoretical utility for glaucoma associated with elevated EVP. A role for netarsudil in patients with elevated EVP is evaluated in a pilot investigation using a cohort of individuals with Sturge-Weber syndrome (SWS). METHODS: Retrospective study of patients with SWS and glaucoma who were treated with netarsudil. Five patients (six eyes) were identified. Data collected included demographics, visual acuity, IOP, glaucoma medical and surgical treatments, and adverse effects of netarsudil. RESULTS: Mean age was 13.6 ± 8.5 years. EVP elevation was presumed based on clinical stigmata and/or historical features. Mean number of baseline glaucoma medications was 3.3 ± 1.2. There was a significant reduction in the IOP at netarsudil initiation (mean 26.2 ± 4.5 mmHg) to 1 month of netarsudil therapy (mean 20.2 ± 3.8 mmHg, p = 0.0283) and latest IOP on netarsudil (mean 17.6 ± 1.4 mmHg, p = 0.0034). Mean duration of netarsudil therapy was 18.7 ± 11.8 months. Three patients required additional glaucoma procedures; one patient required an additional glaucoma medication. Three eyes (50%) developed conjunctival hyperemia. One patient discontinued netarsudil at 29 months, to reduce drop burden. CONCLUSIONS: Netarsudil can effectively reduce IOP in patients with SWS, even when used as a fourth or fifth glaucoma medication. A possible role for netarsudil in the management of patients with elevated EVP is suggested pending further future investigations.

Ocular Surface Disease in Glaucoma Patients.

PURPOSE: To review the most recent studies in the literature regarding the ocular surface in glaucoma patients and treatment options aimed to reduce ocular surface disease in this population. METHODS: We performed a literature search in the electronic databases of PubMed CENT RAL, Google Scholar, EMBASE the Register of Controlled Trials, and Ovid MEDLINE using the following terms: "ocular surface", "dry eye", "glaucoma", "selective laser trabeculoplasty", "glaucoma surgery", "preservatives", "preservative free", "ocular surface disease index", "tear break up time", "MMP-9" and "conjunctival hyperemia". RESULTS: Over the last several years, several studies have demonstrated the changes to the ocular surface in the setting of glaucoma, the best tests for markers of dry eye, and how management can be altered to help address ocular surface disease routinely or in preparation for glaucoma surgery. CONCLUSION: Ocular surface disease in the glaucoma patient population is widely recognized. It should be addressed to maximize patient compliance and quality of life.

Topical netarsudil 0.02% as adjunctive therapy in refractory pediatric glaucoma.

PURPOSE: To evaluate the efficacy of topical netarsudil 0.02% as adjunctive therapy in children with refractory pediatric glaucoma. METHODS: The medical records of patients ≤18 years diagnosed with pediatric glaucoma treated with topical netarsudil 0.02% from June 2019 to March 2022 were reviewed retrospectively. Data collected included age, sex, ethnicity, etiology of glaucoma, history of previous or subsequent glaucoma surgery, and intraocular pressure (IOP) before and after the addition of topical netarsudil. RESULTS: A total of 21 eyes of 16 patients (11 males) were included. Five patients used topical netarsudil in both eyes. Eight patients were Hispanic. The mean number of glaucoma surgeries and medications before initiating topical netarsudil was 1.8 ± 1.2 and 3.7 ± 0.5, respectively. The mean age prior to starting topical netarsudil was 8.9 ± 4.1 years. The mean follow-up after initiating topical netarsudil was 11.3 ± 8.2 months. The IOP was significantly reduced from 26.3 ± 6.2 mm Hg before topical netarsudil to 19.6 ± 6.02 mm Hg at 1 month in 15 eyes (P < 0.01), 18.2 ± 6.9 mm Hg at 3-months in 18 eyes (P < 0.01), 18.3 ± 7.3 mm Hg at 6 months in 13 eyes (P = 0.01), 17.6 ± 5.07 mm Hg at 9 months in 14 eyes (P = 0.002), and 17.4 ± 3.1 mm Hg at 12 months in 13 eyes (P = 0.002). Nine eyes (43%) underwent additional glaucoma surgery due to long-term failure of topical netarsudil to reduce IOP despite an initial reduction, and one eye had persistent IOP elevation ≥21 mm Hg despite the addition of topical netarsudil. CONCLUSIONS: In our small cohort of patients with refractory pediatric glaucoma, the addition of topical netarsudil reduced IOP, potentially delaying the need for surgery.

Congenital cavitary optic disc anomaly and Axenfeld's anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature.

BACKGROUND: Wolf-Hirschhorn syndrome is a rare genetic syndrome caused by a heterozygous deletion on chromosome 4p16.3 and is characterized by a "Greek warrior helmet" facies, hypotonia, developmental delay, seizures, structural central nervous system defects, intrauterine growth restriction, sketelal anomalies, cardiac defects, abnormal tooth development, and hearing loss. A variety of ocular manifestations may occur in up to 40% of patients. MATERIALS/METHODS: We report the genetic testing results, systemic findings, and complete ophthalmologic examination findings in a patient with Wolf-Hirschhorn syndrome, including external photography, RetCam3 (Clarity Medical Systems, Pleasonton, CA) goniography, and fundus photography. In addition, we review the literature on ocular manifestations of Wolf-Hirschhorn syndrome. RESULTS: Microarray analysis revealed an unbalanced translocation between 4p16.3-15.3 and Xp22.33-p22.2. Systemic findings included "Greek warrior helmet" facies, hypotonia, cleft palate, neonatal tooth eruption, talipes equinovarus, bilateral clinodactyly, clitoromegaly, partial agenesis of the corpus callosum, bilateral renal hypoplasia, and two atrial septal defects. Ocular findings included normal intraocular pressures and corneal diameters, large-angle exotropia, downward slanting of the palpebral fissures, absent eyelid creases, upper and lower eyelid retraction with shortage of the anterior eyelid lamellae, euryblepharon, lagophthalmos with poor Bell's reflex and exposure keratopathy, hypertelorism, Axenfeld's anomaly, megalopapillae, and cavitary optic disc anomaly. CONCLUSIONS: We describe the ocular phenotype of a patient with Wolf-Hirschhorn syndrome, including the rare descriptions and photographs of Axenfeld's anomaly, megalopapilla, and cavitary optic disc anomaly in this condition.

The use of irradiated corneal patch grafts in pediatric Ahmed drainage implant surgery.

PURPOSE: To describe the use of irradiated cornea for scleral reinforcement in Ahmed glaucoma valve drainage implant (AGV) devices in children. METHODS: The medical records of patients <18 years of age who underwent AGV surgery with irradiated cornea as scleral reinforcement were reviewed retrospectively. The primary outcome measure was erosion of the drainage tube through the corneal patch graft. Secondary outcome measures included other major complications: persistent inflammation, wound dehiscence, transmission of infectious disease, endophthalmitis, and tube/plate self-explantation. RESULTS: A total of 25 procedures (20 patients) met inclusion criteria. Average patient age was 70 months (range, 2 months to 17 years). Mean follow-up was 24.8 months (range, 6 months to 6.2 years). One tube experienced conjunctival exposure through two separate corneal grafts (2/25 cases [8%]), sequentially in the same eye. The first event occurred at month 3.5 after primary implantation of the tube shunt; the second erosion occurred following revision of the existing implant at month 1.5 postoperatively. There were 2 cases of auto-explantation, 2 cases of wound dehiscence, and 1 case of persistent inflammation. There were no cases of endophthalmitis or other infections. CONCLUSIONS: To our knowledge, this is the first report describing the use of corneal patch grafts in children. Irradiated cornea improves cosmesis and enhances visualization of the tube. The risk of tube exposure was found to be low and comparable to other materials used as a patch graft.

Macular optical coherence tomography in patients with unilateral optic nerve hypoplasia.

PURPOSE: To characterize the extent and location of macular thinning in patients with unilateral optic nerve hypoplasia (ONH) as compared to the contralateral normal eye. METHODS: The medical records of patients with unilateral ONH who underwent spectral domain optical coherence tomography (SD-OCT) of the macula were retrospectively reviewed. SD-OCT scans were manually segmented by 3 observers in 3 macular regions (superior, central, inferior). Boundaries identified included the inner limiting membrane, the junction between the inner nuclear layer and outer plexiform layer, and the neural retina-retinal pigment epithelium interface. Using custom MATLAB software, inner and outer retinal thickness profiles were quantified. A paired t test was used to compare the retinal thickness between the ONH eye and the contralateral normal eyes. RESULTS: Inner retinal thickness of the ONH eye was decreased in all areas of the macula (superior, central, and inferior) compared to the contralateral normal eye (P < 0.05). Outer retinal thicknesses were also decreased in the central and inferior sections compared with the normal eye (P < 0.05). CONCLUSIONS: Optic nerve hypoplasia is a congenital disease known to result in thinning of the nerve fiber and ganglion cell layer. Our small cohort demonstrated thinning of the inner retinal layers as well as the outer retinal layers in the ONH eye compared with the contralateral normal eye.

Immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease.

PURPOSE: To evaluate the prevalence of immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. DESIGN: Matched case-control study. METHODS: Patients with a diagnosis of idiopathic ocular inflammation and family history of inflammatory bowel disease who did not have inflammatory bowel disease themselves were identified and matched to control patients with idiopathic ocular inflammation. Serum was evaluated for immunologic markers using Prometheus IBD Serology 7. Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2 gene associated with Crohn disease. RESULTS: Fifteen patients with idiopathic ocular inflammation and family history of inflammatory bowel disease were matched to 15 control patients based on age, sex, and race. Eight of 15 patients (53%) with a family history of inflammatory bowel disease had elevated p-ANCA antibody levels compared to 3 of 15 controls (20%) (1-sided P = .04) with a matched analysis odds ratio of 6.0 (1-sided P = .06). Four of 15 patients (27%) with family history of inflammatory bowel disease tested positive for immunologic markers predicting ulcerative colitis, while no control patients tested positive (1-sided P = .06). Carrier rates of NOD2 SNPs did not differ significantly between the test and control groups. CONCLUSIONS: One-quarter of patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease had immunologic markers predicting bowel disease, and one-half had elevated p-ANCA levels. Prometheus IBD Serology 7 may be useful in the evaluation of selected patients with unexplained uveitis.

Cord blood nucleated cells induce delayed T cell alloreactivity.

Cord blood (CB) mononuclear cells (MNCs) can be transplanted in HLA mismatched recipients with limited graft rejection or graft-versus-host disease (GVHD). Previous studies have shown that naive T cells and hyporesponsive dendritic cells are largely represented in CB. Data presented here demonstrate that CB MNCs are unable to stimulate allogeneic T cell proliferative or cytotoxic responses in standard in vitro assays. However, a suppressive effect of CB MNCs was ruled out because purified CD34(+) cells or CD14(+) monocytes stimulated T cell responses that were not inhibited by add-back of CB MNCs. The lack of antigen-presenting cell (APC) activity of CB MNCs in primary mixed lymphocyte culture (MLC) did not induce allogeneic T cell anergy. In fact, rechallenge of T cells with CB CD34(+) cells, or immature monocyte-derived dendritic cells (iMo-DCs) in secondary MLC induced potent T cell proliferative responses. A delayed APC activity of CB MNCs was observed after stimulation with irradiated allogeneic T cells for 6 days, likely because of the upregulation of CD86 and HLA-DR on CB cells. Cytotoxic lymphocytes (CTL) were generated after stimulation of blood T cells with CB MNCs for 4 weeks or CB-derived iMo-DCs for 1 week. Concomitant stimulation of T cells with CB iMo-DC obtained from 2 CB units resulted in the generation of CTLs specific for each CB, independently of the CB:CB cell ratio. These data suggest that the APC activity of CB cells possibly increases posttransplant, and may contribute to delayed graft rejection and/or acute and chronic GVHD.

Rapid regression of retinochoroidal venous collaterals following optic nerve sheath fenestration in idiopathic intracranial hypertension.

A woman with idiopathic intracranial hypertension (IIH) experienced rapid regression of retinochoroidal venous collaterals ("optociliary shunt vessels") following optic nerve sheath fenestration. The presence of these vessels is a nonspecific sign of chronic retinal venous compression in patients with optic disc edema including IIH.

Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function.

Dendritic cells (DCs) derive from CD34+ cells or monocytes and stimulate alloimmune responses in transplantation. We hypothesized that the interaction between CD34+ cells and allogeneic T cells would influence the function of hematopoietic stem cells (HSCs). Cord blood (CB) CD34+ cells proliferated briskly in response to allogeneic, but not autologous, T cells when mixed with irradiated T cells for 6 days in vitro. This proliferation was significantly inhibited by an anti-HLA class II monoclonal antibody (mAb), by an anti-TNFalpha mAb, or by CTLA4-Ig. Allogeneic T cells induced the differentiation of CD34+ progenitors into cells with the morphology of dendritic monocytic precursors and characterized by the expression of HLA-DR, CD86, CD40, CD14, and CD11c, due to an endogenous release of TNFalpha. Cotransplantation of CD34+ cells with allogeneic T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells compared with cotransplantation with autologous T cells. In vitro, CD34+ cell-derived antigen-presenting cells (APCs) were functionally capable of both direct and indirect presentation of alloantigens. Based on these findings, we hypothesize that in HSC transplantation the initial cross talk between allogeneic T cells and CD34+ cells may result in the increased generation of APCs that can present host alloantigens and possibly contribute to the development of graft-versus-host disease.

Isolation and characterization of Sphingomonas sp. GTIN11 capable of carbazole metabolism in petroleum.

A bacterial culture was isolated from a manufactured gas plant (MGP) soil based on its ability to metabolize the nitrogen-containing heterocycle carbazole. The culture was identified as a Sphingomonas sp. and was given the designation GTIN11. A cloned 4.2kb DNA fragment was confirmed to contain genes responsible for carbazole degradation. DNA sequence analysis revealed that the fragment contained five open reading frames (ORFs) with the deduced amino acid sequence showing homology to; carbazole terminal dioxygenase (ORF1), 2,3-dihydroxybiphenyl dioxygenase subunits (ORF2 and ORF3), meta-cleavage compound hydrolases (ORF4), and ferrodoxin component of bacterial multicomponent dioxygenases (ORF5). The percent similarity was 61% of these proteins or less to known proteins. The specific activity of Sphingomonas sp. GTIN11 for the degradation of carbazole at 37 degrees C was determined to be 8.0 micromol carbazole degraded/min/g dry cell. This strain is unique in expressing the carbazole degradation trait constitutively. Resting cells of Sphingomonas sp. GTIN11 removed 95% of carbazole and 50% of C1-carbazoles from petroleum in a 16-h treatment time.