Clinical Profile in Genetically Proven Blau Syndrome: A Case Series from South India.

Purpose: To report the clinical profile of genetically proven Blau syndrome in seven cases from a single center in South India.Materials & Methods: Retrospective case seriesResults: There were four females and three males. All cases had a history of skin and joint involvement of varying severity. Flexion contractures of the proximal interphalangeal joints were seen in all cases except Case 2. Ocular involvement was bilateral and included keratoconjunctivitis sicca (six cases), granulomatous panuveitis (three cases), granulomatous anterior uveitis (three cases), conjunctival granulomas (three cases), subepithelial corneal opacities (one case), and subretinal granuloma (one case). Other ocular findings included band-shaped keratopathy (five cases) and cataract (three cases). All cases received oral steroids and methotrexate with an addition of mycophenolate mofetil in one case. Visual prognosis was good in all cases.Conclusions: Blau syndrome is underreported in India. This is the largest case series of genetically proven Blau syndrome from South India and highlights the clinical profile of Blau syndrome seen in India.

Clinical-dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy.

BACKGROUND: Dogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG). HYPOTHESIS/OBJECTIVES: The eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity-modulated radiation therapy (IMRT). ANIMALS: Dogs with nasal tumors treated with RT between August 2013 and December 2016. METHODS: Case control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow-up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs. RESULTS: Twenty-five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84-122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75-42.33) for KCS eyes and 10.33 Gy (1.8-24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy. CONCLUSION AND CLINICAL IMPORTANCE: Contouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca and salivary gland dysfunction in patients with Sjögren's syndrome: a longitudinal analysis of the Korean Initiative of primary Sjögren's Syndrome (KISS) cohort.

OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.

A Review of Ocular Graft-Versus-Host Disease.

: Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic hematopoietic stem cell transplantation, which is a potential curative therapy used in a variety of malignant or benign hematological diseases. Graft-versus-host disease primarily occurs in many organs, but most notably in the skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal system. Ocular manifestations of GVHD may precede other systemic GVHD findings, and it may be a poor prognosis for mortality. While all parts of the eye may be affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or keratoconjunctivitis sicca is the most common presenting manifestation of chronic ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability. Depending on the severity of ocular involvement and response to treatment, ocular GVHD may cause decreased quality of life. Management of GVHD begins with prevention by understanding risk factors and by implementing prophylactic treatment after allogeneic hematopoietic stem cell transplantation. A multidisciplinary approach to the prevention and treatment of GVHD is important, and there are currently no preventive therapies available for ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular surface lubrication and support, tear film stabilization, inflammation reduction, and surgical intervention. The goal of this review is to define ocular GVHD and its categorical manifestations, as well as to describe the importance of comprehensive assessment, diagnosis, and ophthalmologic treatment and management of ocular GVHD with a multidisciplinary approach.

Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC.

Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P<0.001), the mean Oxford score (3.2 versus 1.3, respectively, P<0.001) as well as visual acuity (Log MAR of 0.33 versus 0.10, respectively, P<0.001). Treatment with scleral lenses was discontinued in only 5 patients (8%) with a median follow-up of 20.5 months (range: 2-125 months). Scleral lenses were very efficient and well tolerated in patients with severe cGvHD-related KCS.

Systemic lupus erythematosus: An update for ophthalmologists.

Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition that may affect almost any part of the eye. We provide an update for the practicing ophthalmologist comprising a systematic review of the recent literature presented in the context of current knowledge of the pathogenesis, diagnosis, and treatment of this condition. We review recent advances in the understanding of the influence of genetic and environmental factors on the development of SLE. Recent changes in the diagnostic criteria for SLE are considered. We assess the potential for novel molecular biomarkers to find a clinical application in disease diagnosis and stratification and in the development of therapeutic agents. We discuss limited forms of SLE and their differentiation from other collagen vascular disorders and review recent evidence underlying the use of established and novel therapeutics in this condition, including specific implications regarding monitoring for ocular toxicity associated with antimalarials.

[Gas-permeable scleral lens for management of severe keratoconjunctivitis sicca secondary to chronic graft-versus-host disease]. / Traitement des sécheresses oculaires sévères secondaires à la maladie du greffon contre l'hôte chronique par lentilles sclérales perméables à l'oxygène.

INTRODUCTION: Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation. Severe keratoconjunctivitis sicca is common in patients with chronic GVH disease. The goal of this study was to evaluate the safety and efficacy of a gas-permeable scleral lens in the management of severe dry eye disease associated with chronic GVH. PATIENTS AND METHODS: This is a retrospective study from June 2009 to November 2013. Patients fitted with scleral lenses for severe keratoconjunctivitis sicca associated with chronic GVH were included. The main outcomes measured were best-corrected visual acuity and quality of life (OSDI and NEI-VFQ25) composite scores before and six months after scleral lens fitting. RESULTS: Sixteen patients were included. The mean age was 52 years (19-69 years). Mean follow-up was 20 months (3-48 months). All patients reported improvement of their ocular symptoms. Best corrected visual acuity improved from 0.21 ± 0.26 to 0.1 ± 0.14 logMAR (P = 0.002), OSDI score improved from 92.1 ± 11.3 to 23.5 ± 11.2 (P = 0.002) and NEI-VFQ25 improved from 41.3 ± 7 to 83.1 ± 15.9 (P = 0.003), 6 months after scleral lens fitting. No serious adverse events, infectious, hypoxemic or allergic complications attributable to the scleral lens occurred. CONCLUSION: Gas-permeable scleral lens use appears to be safe and effective in patients with severe dry eye related to chronic GVH.

Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem cell transplantation.

We analyzed the incidence and risk factors for ocular GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Korea. In this retrospective, noncomparative, observational study, 635 subjects were included who had at least 2 years of follow-up ophthalmological examinations after allo-HSCT from 2009 to 2012 at Seoul St Mary's Hospital, Seoul, Korea. The mean duration between allo-HSCT and onset of ocular GVHD was 225.5±194.3 days. The adjusted incidence for acute ocular GVHD was 1.33% and that for chronic GVHD was 33.33%. In the multivariate analysis, preexisting diabetes mellitus (odds ratio (OR): 4.22, 95% confidence interval (CI): 1.66-10.72), repeated allo-HSCT (OR: 29.10, 95% CI: 1.02-8.28) and the number of organs that chronically developed GVHD by stage I (OR: 14.63, 95% CI: 9.81-21.84) increased risk of ocular GVHD. Careful monitoring of ocular GVHD is needed in patients with chronic GVHD in multiple organs and preexisting diabetes.

Retrospective study of the prevalence of keratoconjunctivitis sicca in diabetic and nondiabetic dogs after phacoemulsification.

OBJECTIVE: To evaluate the prevalence of keratoconjunctivitis sicca (KCS) in diabetic and nondiabetic dogs following phacoemulsification. PROCEDURES: Medical records were reviewed for signalment, body weight, diabetes status, and STT at the preoperative and all postoperative examinations. A clinical diagnosis of KCS was defined as a STT <15 mm/min with compatible clinical signs. Schirmer tear test values and the prevalence of KCS based on STT <15 mm/min were evaluated at 2-4, 5-8, 9-14, 15-20, and 41-52 weeks postoperatively. Size of dog (large, >10 kg; small, ≤10 kg) and STT ranges (<15 mm/min, 15-22 mm/min and >22 mm/min) were categorized for analysis of effect of body weight and STT on prevalence of KCS. RESULTS: One hundred and seventeen nondiabetic (198 eyes) and 118 diabetic dogs (228 eyes) were evaluated. KCS was diagnosed in nearly twice as many diabetics as nondiabetics (27.4% vs. 15.4%) within 2 weeks postoperatively (P = 0.0088). Percentage of eyes with KCS among all dogs decreased over time and did not differ significantly after the first postoperative visit. Diabetic small dogs were 1.7 times more likely to have KCS than nondiabetic small dogs (P = 0.0052). Preoperative STT was significantly associated with likelihood of postoperative KCS among large (P < 0.0001), but not small dogs (P = 0.0781). Among large dogs, eyes with STTs between 15 and 22 mm/min were approximately 3 times more likely to be diagnosed with KCS after surgery than those with STT >22 mm/min. CONCLUSION: The greatest risk for KCS for all dogs is during the first 2 weeks postoperatively. Populations at greatest risk for postoperative KCS are small dogs, small diabetic dogs, and large dogs with preoperative STT ≤22.

Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease.

PURPOSE: The aim of this study was to establish and characterize extraorbital lacrimal gland excision (LGE) as a model of aqueous tear-deficient dry eye disease in mice. METHODS: Female C57BL/6 mice at 6 to 8 weeks of age were randomized to extraorbital LGE, sham surgery, or scopolamine groups. Mice that underwent extraorbital LGE or sham surgery were housed in the standard vivarium. Scopolamine-treated mice were housed in a controlled environment chamber that allowed for the continuous regulation of airflow (15 L/min), relative humidity (30%), and temperature (21-23°C). Clinical disease severity was assessed over the course of 14 days using the phenol red thread test and corneal fluorescein staining. Real-time polymerase chain reaction was performed to assess corneal mRNA expression of interleukin 1ß, tumor necrosis factor α, and matrix metalloproteinase 9. Flow cytometry was used to assess T helper cell frequencies in the conjunctivae and draining lymph nodes. RESULTS: Extraorbital LGE markedly reduced aqueous tear secretion as compared with the sham procedure and induced a more consistent decrease in aqueous tear secretion than was observed in mice that received scopolamine while housed in the controlled environment chamber. Extraorbital LGE significantly increased corneal fluorescein staining scores as compared with those of both the sham surgery and scopolamine-treated groups. Extraorbital LGE significantly increased the corneal expression of interleukin 1ß, tumor necrosis factor α, and matrix metalloproteinase 9. Further, extraorbital LGE increased T helper 17-cell frequencies in the conjunctivae and draining lymph nodes. CONCLUSIONS: Extraorbital LGE induces aqueous tear-deficient dry eye disease in mice as evidenced by decreased aqueous tear secretion, increased corneal epitheliopathy, and induced ocular surface inflammation and immunity.

New therapies in common ocular surface disorders.

Lacrimal dysfunction syndrome (LDS) and meibomian gland dysfunction (MGD) are common pathologies of the ocular surface both characterized by quantitative and/or qualitative tear film changings. They may result in symptoms of eye irritation, clinically apparent inflammation and ocular surface disease. Recent researches about the chronic inflammatory nature of dry eye, revealed the possibility to develop new treatments for LDS like new immunological drugs. MGD, alone or if it occurs contemporary to LDS, can be treated with a thermal pulsation system, a useful tool to alleviate symptoms.

Corneal ulceration in a LASIK patient due to vitamin a deficiency after bariatric surgery.

PURPOSE: To review the case of a 41-year-old woman who underwent bariatric surgery in 2000. She subsequently underwent laser in situ keratomileusis (LASIK) surgery in 2008 and complained of dry eye since the LASIK surgery. In November 2010, she was diagnosed with a corneal melt and was treated with aggressive lubrication, followed by eventual amniotic membrane placement and a tarsorrhaphy. She then presented for consultation at the Bascom Palmer Eye Institute when she developed a corneal infiltrate. She was diagnosed with fungal keratitis with corneal xerosis. At that time, vitamin A levels were measured and were less than 2 µ/dL. The patient admitted noncompliance with nutritional supplements. METHODS: Case report. RESULTS: The patient was treated with aggressive lubrication and natamycin. Vitamin supplements were restarted, and the patient experienced dramatic improvement in symptoms with resolution of the infection. A central corneal scar with corneal thinning remains. The patient underwent a penetrating keratoplasty for visual rehabilitation. CONCLUSIONS: Patient education with emphasis on compliance with nutritional supplements is essential after bariatric surgery. Consider vitamin A deficiency in the differential diagnosis of dry eye after LASIK surgery.

Interleukin-1 receptor mediates the interplay between CD4+ T cells and ocular resident cells to promote keratinizing squamous metaplasia in Sjögren's syndrome.

Keratinizing squamous metaplasia (SQM) of the ocular mucosal epithelium is a blinding corneal disease characterized by the loss of conjunctival goblet cells (GCs), pathological ocular surface keratinization and tissue recruitment of immune cells. Using the autoimmune regulator (Aire)-deficient mouse as a model for Sjögren's syndrome (SS)-associated SQM, we identified CD4(+) T lymphocytes as the main immune effectors driving SQM and uncovered a pathogenic role for interleukin-1 (IL-1). IL-1, a pleiotropic cytokine family enriched in ocular epithelia, governs tissue homeostasis and mucosal immunity. Here, we used adoptive transfer of autoreactive CD4(+) T cells to dissect the mechanism whereby IL-1 promotes SQM. CD4(+) T cells adoptively transferred from both Aire knockout (KO) and Aire/IL-1 receptor type 1 (IL-1R1) double KO donors conferred SQM to severe-combined immunodeficiency (scid) recipients with functional IL-1R1, but not scid recipients lacking IL-1R1. In the lacrimal gland, IL-1R1 was primarily immunolocalized to ductal epithelium surrounded by CD4(+) T cells. In the eye, IL-1R1 was expressed on local mucosal epithelial and stromal cells, but not on resident antigen-presenting cells or infiltrating immune cells. In both tissues, autoreactive CD4(+) T-cell infiltration was only observed in the presence of IL-1R1-postive resident cells. Moreover, persistent activation of IL-1R1 signaling led to chronic immune-mediated inflammation by retaining CD4(+) T cells in the local microenvironment. Following IL-1R1-dependent infiltration of CD4(+) T cells, we observed SQM hallmarks in local tissues-corneal keratinization, conjunctival GC mucin acidification and epithelial cell hyperplasia throughout the ocular surface mucosa. Proinflammatory IL-1 expression in ocular epithelial cells significantly correlated with reduced tear secretion, while CD4(+) T-cell infiltration of the lacrimal gland predicted the development of ocular SQM. Collectively, data in this study indicated a central role for IL-1 in orchestrating a functional interplay between immune cells and resident cells of SS-targeted tissues in the pathogenesis of SQM.

Dacryocystorhinostomy precipitating keratoconjunctivitis sicca in aplasia of lacrimal and major salivary glands (ALSG).

We report a 16-month-old girl referred for bilateral epiphora and sticky eyes since birth. Examination revealed a refluxible left lacrimal sac mucocele, agenesis of the left lower punctum, and agenesis of both puncta on the right side. Complete bony obstruction was noted on probing of the left nasolacrimal duct. At 4 years of age, she underwent left external dacryocystorhinostomy (DCR) with silicone intubation because of chronic dacryocystitis. Her epiphora and stickiness improved significantly in the first postoperative year, but she subsequently developed dryness of the left eye, dry mouth, and dental caries. CT and MRI scans revealed the absence of the lacrimal and salivary glands. The clinical signs and symptoms improved with plugging the left upper punctum and topical lubricants. Aplasia of the lacrimal and salivary glands may present with symptoms of congenital lacrimal obstruction, and failure to make an early diagnosis will result in inappropriate lacrimal surgery and dry eye.

Prevalence of eye disease in Brazilian patients with psoriatic arthritis

OBJECTIVES: The aim of this study was to report the type and frequency of ocular manifestations in Brazilian psoriatic arthritis patients. METHODS: We conducted a cross-sectional study in a Brazilian tertiary hospital. The test group included 40 patients who had psoriatic arthritis according to the Classification Criteria for Psoriatic Arthritis. A control group of 40 individuals was matched for age and gender. All of the patients underwent ophthalmic evaluation, which included best-corrected visual acuity, slit lamp and fundus examinations, and dry eye diagnostic tests (Schirmer I, tear breakup time and rose bengal). Demographic parameters were also evaluated. RESULTS: The mean age of the patients was 53.9±13.1 years; the mean disease duration was 8±10.5 years. Most of the patients were women (60%), and the majority had polyarticular disease (57.5%). Several ocular abnormalities were found, including punctate keratitis, pinguecula, blepharitis, pterygium, cataract, glaucoma, uveitis, and retinal microvascular abnormalities. There were no significant differences in the rates of these abnormalities compared with the control group, however. The Keratoconjunctivitis sicca and dry eye diagnostic tests were more often positive in the patients with psoriatic arthritis than in the control group. CONCLUSIONS: In this study, keratoconjunctivitis sicca was the most common ocular finding related to psoriatic arthritis. Therefore, we recommend early ophthalmologic evaluations for all psoriatic arthritis patients who complain of eye symptoms.

[Ocular involvement and its' manifestations in rheumatoid arthritis patients].

PURPOSE: To study the type, occurrence and nature of ocular involvement amongst patients with rheumatoid arthritis (RA), and to identify demographic, clinical and/or laboratory variables associated with eye involvement in RA. RESEARCH TYPE: Cross sectional research, retrospective METHODS: The research was conducted among 61 patients diagnosed with rheumatoid arthritis. The subjects were recruited for the research during their periodic visits to the Soroka Hospital Rheumatology Clinic. Comprehensive rheumatologic tests were administered and general health was examined with a prepared questionnaire. Additionally, the subjects' personal files were examined with data collected from general serum rheumatologic tests and details regarding medications administered. The patients were given a comprehensive eye examination, including a visual acuity examination, test for anterior and posterior fragments, a slit lamp examination after pupil dilation, for epithelial cell filaments, tests for dry eye symptoms, including a Schirmer's test, a tear breakup time test, and a corneal examination for epithelial cells and the existence of superficial punctate keratopathy. The subjects were also questioned regarding their dry eye syndrome and a specular microscopy test was performed. The assembled data was processed and analyzed with the aim of finding correlations between the subjective and objective sensations of dry eye symptoms and the activity of rheumatoid arthritis disease, blood tests, medications taken, and the patient's general state of health. RESULTS: The majority of the research subjects (90.2%) were women. Their average age was 51.9 +/- 13.21 years; 31.1% of the subjects complained of eye dryness and, during the eye examination, 85% were found to be suffering from dry eye. The study found a correlation between the objective indicators of keratitis sicca and the following parameters: laboratory values for SGOT (p < 0.03), ESR (p < 0.05), Cr (p < 0.05), TG (p < 0.03), LDL (p < 0.02), Hb (p < 0.01), ALP (p < 0.01), in addition to prednisone medication (p < 0.03, df = 2, x2 = 7.02) and methotrexate (p < 0.03, df = 2, x2 = 8.88). No correlation was found with the following parameters: age, disease duration, smoking, disease severity, other background diseases, and additional laboratory findings including RF and ANA measurements, and consuming other anti-rheumatoid arthritis medications. Similarly, no relation was found with the patients' various subjective syndromes. The average results of the specular microscopy test were 2116.15 +/- 416.59 for the right eye and 2125.67 +/- 446.14 for the left eye. CONCLUSIONS: The significance of the specular microscopy test results is that corneal damage found in rheumatoid arthritis patients occurs only to the external layer and does not affect the endothelial layer. The study indicates that keratitis sicca is prevalent among rheumatoid arthritis patients and must be taken into account regardless of the degree that the disease has progressed, because the severity of the dryness is not dependent on disease progression. Additionally, a discrepancy exists between the patients' subjective sensation of their eye condition and the objective findings of the study.