Janine A. Smith

Grading of corneal and conjunctival staining in the context of other dry eye tests.

Purpose To describe the Oxford Scheme for grading ocular surface staining in dry eye and to discuss optimization of stain detection using various dyes and filters. Also, to propose a sequence of testing for dry eye diagnosis. Methods The grading of corneal and conjunctival staining is described, using the Oxford Scheme, including biomicroscopy, optical filters, illumination conditions, and the characteristics of and instillation techniques used for, selected clinical dyes. Results A series of panels, labeled A–E, in order of increasing severity, reproducing the staining patterns encountered in dry eye, are used as a guide to grade the degree of staining seen in the patient. The amount of staining seen in each panel, represented by punctate dots, increases by 0.5 of the log of the number of dots between panels B to E. The use of the vital dyes fluorescein, lissamine green, and rose Bengal is described; fluorescein and lissamine green, used in conjunction with appropriate absorption filters, are recommended for use in clinical trials. The placement of staining in relation to the sequence of other diagnostic tests is discussed. Conclusions The monitoring and assessment of corneal and conjunctival staining can be greatly enhanced by the use of a grading scale, controlled instillation of dyes, and standard evaluation techniques. This is of particular benefit in clinical trials, where ocular surface staining is commonly employed as an outcome measure

Epidemiology and Course of Disease in Childhood Uveitis

PURPOSE To describe the disease characteristics and visual outcome of pediatric uveitis. DESIGN Retrospective, longitudinal observation. PARTICIPANTS Five hundred twenty-seven pediatric uveitis patients from the National Eye Institute, University of Illinois, Chicago, and Oregon Health Sciences University. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Demographics, uveitis disease characteristics, complications, treatments, and visual outcomes were determined at baseline and at 1-, 3-, 5-, and 10-year time points. RESULTS The patient population was 54% female; 62.4% white, 12.5% black, 2.7% Asian, 2.1% multiracial, and 14.61% Hispanic. Median age at diagnosis was 9.4 years. The leading diagnoses were idiopathic uveitis (28.8%), juvenile idiopathic arthritis-associated uveitis (20.9%), and pars planitis (17.1%). Insidious onset (58%) and persistent duration (75.3%) were most common. Anterior uveitis was predominant (44.6%). Complications were frequent, and cystoid macular edema (odds ratio [OR] 2.94; P = 0.006) and hypotony (OR, 4.54; P = 0.026) had the most significant visual impact. Ocular surgery was performed in 18.9% of patients. The prevalence of legal blindness was 9.23% at baseline, 6.52% at 1 year, 3.17% at 3 years, 15.15% at 5 years, and 7.69% at 10 years. Posterior uveitis and panuveitis had more severe vision loss. Hispanic ethnicity was associated with a higher prevalence of infectious uveitis and vision loss at baseline. CONCLUSIONS The rate and spectrum of vision threatening complications of pediatric uveitis are significant. Prospective studies using standard outcome measures and including diverse populations are needed to identify children most at risk.

Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren's syndrome-related dry eye

BackgroundTo examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögrens syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth.MethodsForty-two patients fulfilling European / American diagnostic criteria for Sjögrens syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales.ResultsParticipants (aged 31–81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (ρ) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (ρ = 0.32, p = .05) and for the distance vision subscale with van Bijsterveld score (ρ = 0.33, p = .04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (ρ = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (ρ = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively).ConclusionsAssociations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögrens syndrome-related dry eye on VT-HRQ.

Mutations in PIP5K3 Are Associated with François-Neetens Mouchetée Fleck Corneal Dystrophy

François-Neetens fleck corneal dystrophy (CFD) is a rare, autosomal dominant corneal dystrophy characterized by numerous small white flecks scattered in all layers of the stroma. Linkage analysis localized CFD to a 24-cM (18-Mb) interval of chromosome 2q35 flanked by D2S2289 and D2S126 and containing PIP5K3. PIP5K3 is a member of the phosphoinositide 3-kinase family and regulates the sorting and traffic of peripheral endosomes that contain lysosomally directed fluid phase cargo, by controlling the morphogenesis and function of multivesicular bodies. Sequencing analysis disclosed missense, frameshift, and/or protein-truncating mutations in 8 of 10 families with CFD that were studied, including 2256delA, 2274delCT, 2709C-->T (R851X), 3120C-->T (Q988X), IVS19-1G-->C, 3246G-->T (E1030X), 3270C-->T (R1038X), and 3466A-->G (K1103R). The histological and clinical characteristics of patients with CFD are consistent with biochemical studies of PIP5K3 that indicate a role in endosomal sorting.

Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin.

Purpose: To evaluate the modulatory effects of anti-inflammatory agents, dexamethasone (Dex) and cyclosporin A (CsA), on the production of cytokines and chemokines by human corneal cells in vitro following stimulation by the pro-inflammatory cytokine after interleukin 1β (IL-1β). Methods: A human corneal epithelial (HCE) cell line and human corneal fibroblasts (HCFs) were stimulated in culture with IL-1β and treated with Dex or CsA. The gene expression for selected cytokines and chemokines was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of cytokines and chemokines was measured by enzyme-linked immunosorbent assay. Results: IL-1β enhanced the mRNA and/or protein levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, and monocyte chemotactic protein (MCP)-1 in HCE and IL-6, IL-8, MCP-3, and regulated on T-cell activation expressed secreted (RANTES) in HCFs. Treatment with CsA did not inhibit cytokine production in either HCE or HCFs. In contrast, Dex treatment inhibited the IL-1β-induced production of GM-CSF, IL-6, IL-8, MCP-3, and RANTES, but not MCP-1. Conclusion: These results show that Dex, but not CsA, has direct immunosuppressive effects on the resident corneal cells, HCE and HCFs. This suggests that the clinically observed immunosuppressive effects of topical CsA are mediated primarily through the immune cells.

Menisci and fullness of the blink in dry eye.

Purpose. This study was to investigate the role of the upper meniscus in tear film formation and blinking. Methods. One microliter of 2% fluorescein was instilled under the upper lid of 15 dry eye (DE) and 15 control subjects. Subjects were instructed to blink partially and hold the eye open as long as possible, and analysis of tear breakup dynamics was used to quantify the area of breakup. This procedure was repeated following a full blink. Meniscus height was measured from digital videos. Results. Both menisci were significantly decreased in DE compared with controls (p < 0.02, t test). Tear breakup dynamics analysis showed that significantly greater areas of breakup occurred with full compared with incomplete blinks in DE (p < 0.003 Mann Whitney U test), but not in controls. Conclusions. A stable tear film can be deposited by the upper meniscus alone following a partial blink, without contribution from the lower meniscus. The increased tear stability of partial blinks in DE may be due to less stretching of the already fragile tear film compared with a full blink, which covers more surface area.

Intraocular Levels of Methotrexate After Intravenous Administration

PURPOSE To determine if adequate intraocular levels of methotrexate are achieved after intravenous administration. METHODS After intravenous administration, methotrexate levels were determined in the serum, the anterior chamber, and the cerebrospinal fluids of a patient with recurrent ocular lymphoma. A fluorescence polarization immunoassay was used to make the determinations. RESULTS At seven hours into a 24-hour intravenous infusion, methotrexate was at cytotoxic level in all samples. At 74 hours, cytotoxic levels were present only in the aqueous humor. CONCLUSION Sustained cytotoxic ocular methotrexate levels are achievable after systemic administration.

Orbital socket contracture: a complication of inflammatory orbital disease in patients with Wegener’s granulomatosis

Aim: To describe the clinical characteristics of orbital socket contracture in patients with Wegener’s granulomatosis (WG). Methods: A retrospective cohort study The medical records of 256 patients with WG examined at the National Institutes of Health from 1967 to 2004 were reviewed to identify patients with orbital socket contracture. Details of the orbital disease including Hertel exophthalmometry readings, radiological findings, and results of eye examinations were recorded. Orbital socket contracture was defined as orbital inflammation with proptosis followed by the development of enophthalmos and radiographic evidence of residual fibrotic changes in the orbit. To examine for risk factors in the development of a contracted orbit, patients with orbital socket contracture were compared to patients without contracture with respect to multiple variables including history of orbital surgery, orbital disease severity, and major organ system involvement. The main outcome measures were the clinical characteristics of orbital socket contracture associated with inflammatory orbital disease in patients with WG. Results: Inflammatory orbital disease occurred in 34 of 256 (13%) patients and detailed clinical data on 18 patients were available and examined. Orbital socket contracture occurred during the clinical course in six patients; the features included restrictive ophthalmopathy (five), chronic orbital pain (three), and ischaemic optic nerve disease (two) resulting in blindness (no light perception) in one patient. The orbital socket contracture occurred within 3 months of treatment with immunosuppressive medications for inflammatory orbital disease in five patients and was not responsive to immunosuppressive medications. The median degree of enophthalmos in the contracted orbit compared with the fellow eye was 2.8 mm (range 1.5–3.5 mm) by Hertel exophthalmometry. There were no risk factors that predicted development of orbital socket contracture. Conclusions: In six patients with WG and active inflammatory orbital disease, orbital socket contracture occurred during the treatment course with systemic immunosuppressive medications. The orbital socket contracture, presumably caused by orbital fibrosis, led to enophthalmos, restrictive ophthalmopathy, chronic orbital pain, and optic nerve disease and was not responsive to immunosuppressive therapy. Orbital socket contracture has not been previously reported as a complication of inflammatory orbital disease associated with WG and was an important cause of visual morbidity in our cohort of patients.

Noninvasive diagnosis and ophthalmic features of mucolipidosis type IV

OBJECTIVE To comprehensively describe the ophthalmic characteristics of patients with mucolipidosis type IV. DESIGN Prospective natural history study. PARTICIPANTS Twenty-two patients with confirmed mucolipidosis type IV. METHODS OR TESTING: External and slit-lamp examination with dilated funduscopy, photography of corneal and retinal lesions, and exfoliative conjunctival cytology were performed. MAIN OUTCOME MEASURES Grading of corneal, optic nerve, retinal vasculature, and pigmentary abnormalities. RESULTS All patients exhibited some degree of corneal epithelial haze, optic nerve pallor, retinal vascular attenuation, and retinal pigment epithelial changes. The associated ocular findings observed in decreasing order of frequency were strabismus, corneal erosion, cataract, corneal abnormalities, fundus abnormalities, and ptosis. The older patients were significantly more likely to demonstrate severe optic nerve pallor, retinal vascular attenuation, and corneal epithelial haze. Conjunctival cytologic studies showed characteristic lysosomal inclusions on light and electron microscopy. CONCLUSIONS Patients with mucolipidosis type IV have characteristic ophthalmic features, most of which have a progressive course. Conjunctival cytologic studies help confirm the diagnosis of this disorder.

Corneal endothelial deposits in children positive for human immunodeficiency virus receiving rifabutin prophylaxis for mycobacterium avium complex bacteremia

PURPOSE To assess the potential ocular effects of prophylactic administration of rifabutin in children with symptomatic human immunodeficiency virus (HIV) infection and CD4 counts less than 50 cells per mm3. METHODS Twenty-five children with HIV infection were enrolled in a phase I-II study of prophylactic administration of systemic rifabutin for prevention of disseminated Mycobacterium avium complex infection and monitored prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. RESULTS The dose of rifabutin ranged from 5.0 mg to 15.0 mg per kg, and the median ophthalmic follow-up was 24 months. During the study period, six of the children receiving rifabutin prophylaxis for M. avium complex developed unusual bilateral, initially peripheral, stellate, corneal endothelial deposits without associated uveitis. Review of serial corneal drawings and photographs showed an increase in the number of corneal deposits with continued administration of rifabutin. The duration of rifabutin treatment (P = .017) and follow-up (P = .0011) was significantly longer in patients who developed these corneal endothelial changes. CONCLUSION Corneal endothelial deposits should be considered a potential side effect of rifabutin therapy. To date, these findings have not been sight threatening.