T Regulatory Cells in Rheumatoid Arthritis with Reference to Anti-Citrullinated Peptide Antibody and TNF-alpha Inhibitor Therapy.

T regulatory cells (Tregs) plays an important role in maintaining self-tolerance and preventing autoimmune diseases by inhibiting proliferation and cytokine production of self-reactive T cells. Controversy was reported regarding the frequency of CD4+CD25+ Tregs in the peripheral circulation of rheumatoid arthritis (RA) patients compared to normal controls. Also, some showed that treatment with TNF-α inhibitor restored the capacity of Tregs. This work aimed to study Tregs in the peripheral blood of RA patients versus control in addition to those on TNF-α inhibitor therapy compared to those who have not received it and to correlate with status of anti-cyclic citrullinated peptide antibody (ACPA). Two groups of RA patients were studied; one on TNF-α inhibitor therapy and the other not. Additionally, age-matched apparently healthy controls were studied. The percentage of CD4+CD25+ T cells in the total lymphocytic cell population was determined by flow cytometry analysis while ACPA concentration was measured by a second-generation peptide-based ELISA. Mean level of Tregs was significantly lower in the studied RA patients compared to the control group. Patients in early disease (0-5 years) had low mean Tregs percentage compared to patients with long duration of disease (> 10 years) (P=0.044). Patients on TNF-α blocker therapy had elevated Tregs percentage relative to patients on methotrexate (MTX) (P=0.022) and other therapies. No effect of gender or age was found on Tregs levels. In RA patients, 85.4% were ACPA seropositive and 65.9% of seropositive patients have concentration of > 100U/ml. The mean Treg percentage was significantly lower in ACPA seronegative group compared to the seropositive group (P=0.013). In conclusion, the studied RA patients have low Treg, and TNF-α blocker therapy increased its number, compared to other therapies.

Aqueous penetration of topical tacrolimus.

PURPOSE: To evaluate the penetration of topical tacrolimus 0.05% into the aqueous humor. OBSERVATIONS: A total of four patients scheduled for routine cataract surgery were included prospectively. We excluded patients with corneal pathology or ocular surface diseases. Topical tacrolimus 0.05% was compounded at our facility. It was dosed every 1 min for 5 min an hour before the aqueous was sampled. Aqueous samples were collected at the time of cataract surgery and were subjected to detection of presence and level of tacrolimus. There were 2 male and 2 female patients. The age range was 58-73 years with a mean age of 66 years. Tacrolimus was detected in the aqueous humor in all patients. The concentration of tacrolimus in the aqueous ranged from 2.6 to 5.6 ng/ml (mean 4.15 ± 1.18 ng/ml). In all patients, the aqueous tacrolimus concentration was greater than the minimal therapeutic level. The study was registered at clinicaltrials.gov (registration number is NCT02794610). CONCLUSIONS AND IMPORTANCE: Tacrolimus was detected in the aqueous humor following topical application. Topical tacrolimus may be a promising steroid-sparing modality for the treatment of anterior uveitis.

Hydroxychloroquine dosing and toxicity: A real-world experience in Saudi Arabia of 63 patients.

PURPOSE: To assess the ocular toxicity in patients on high doses of hydroxychloroquine (HCQ) per weight, as per the latest American Academy of Ophthalmology (AAO) screening guidelines for HCQ toxicity. METHODS: This is a multi-center study looking at consecutive patients attending the ophthalmology clinics at a tertiary hospital and a private clinic in Saudi Arabia. A data collection sheet was used to collect patient's information regarding the dose per body weight, duration of HCQ use and any risk factors associated with the use of the medication as per the latest AAO guidelines for HCQ screening. Ancillary testing including fundus photography, automated visual field (10-2) and spectral domain ocular coherence tomography were done. Further testing with fundus auto-fluorescence and multifocal ERG were done when needed. The presence or absence of toxicity was recorded. RESULTS: A total of 63 patients were included in the study, 58 females and 5 males. The average patient age was 45 years (range 18-72). The mean dosage of HCQ was 3.9 mg/kg. Fourteen (22%) patients were on doses higher than 5 mg/kg. The duration of treatment ranged from 1-30 years (average 8.3). Thirty six (57%) patients were on the drug for more than 5 years. We found only one (1.58%) patient with HCQ toxic retinopathy over a mean of 8 years treatment period. CONCLUSION: A significant number of our patients were found to be on doses of >5 mg/kg of HCQ, which may put them at a higher risk for retinal toxicity. Low dose HCQ such as 100 mg tablets should be made available to help physicians in adjusting the dose as per the latest reported guidelines by the AAO.

Incidence of posterior capsule opacification following phacoemulsification in patients with uveitis.

PURPOSE: The purpose of this study was to evaluate the incidence of posterior capsule opacification (PCO) in patients with inactive uveitis who underwent phacoemulsification with acrylic hydrophobic intraocular lens. METHODS: Thus was a retrospective review of 25 consecutive patients (31 eyes) with uveitis who underwent phacoemulsification. A group of 100 patients (140 eyes) without uveitis served as historical controls. RESULTS: In patients with uveitis, PCO occurred in 11 eyes (35.5%), 6 (19%) of which were visually significant and required treatment with neodymium-doped yttrium aluminum garnet (Nd: YAG) laser. In the control group, PCO developed in 17 (12%) eyes which required treatment with Nd: YAG laser. The incidence of PCO was significantly higher in uveitis patients compared to the control group (P = 0.001), but the incidence of visually significant PCO requiring laser capsulotomy was not statistically significant (P = 0.3). CONCLUSION: The incidence of PCO in patients with uveitis was significantly higher than those without uveitis, but the need for Nd: YAG laser capsulotomy for visually significant PCO was not statistically significant.

Topical Tacrolimus in Thygeson Superficial Punctate Keratitis.

PURPOSE: To evaluate the efficacy of topical tacrolimus 0.02% eye drops in the treatment of patients with Thygeson superficial punctate keratitis. METHODS: Ten consecutive patients with Thygeson superficial punctate keratitis were included retrospectively. Seven patients were unresponsive to topical steroids and/or lubricants. Diagnosis was made based on the history and clinical findings. All patients were treated with topical tacrolimus 0.02% solution twice daily. Outcome measures included improvement in symptoms of tearing and photophobia, whereas improvement in signs included decrease in the number of the lesions, resolution of the lesions, flattening of the lesions, and decrease in stain of the lesions. RESULTS: There were 3 male and 7 female patients with an age range of 3 to 51 years (mean 17 years). All patients had bilateral ocular involvement. Duration of treatment ranged from 1 to 42 weeks (mean 10 weeks). All patients had subjective improvement in symptoms of tearing and photophobia and resolution of the superficial punctate keratitis. The response to treatment was noted 72 hours after initiation of therapy in all patients. Topical tacrolimus was well tolerated in all patients. CONCLUSIONS: Topical tacrolimus 0.02% is safe and effective in reducing ocular surface inflammation in patients with Thygeson superficial punctate keratitis who are not responsive to conventional therapy. Tacrolimus is helpful as a steroid-sparing agent to avoid vision-threatening complications.

Assessment of Ophthalmology Residency Programs in Saudi Arabia: A Trainee-Based Survey.

PURPOSE: To assess the satisfaction and competency of Saudi ophthalmology residents and compare their performance against International Council of Ophthalmology (ICO) standards. METHODS: A cross-sectional web-based survey of senior ophthalmology residents (postgraduate years [PGY] 3-4) and recent graduates (from 2010 to 2015) assessed various aspects of training. The questionnaire was sent to the participants and was divided into 3 main domains: demographics, training program evaluation, and preparedness for board exams and clinical practice. RESULTS: Out of the 145 invitees, 120 (82.8%) responded. Fifty percent of respondents reported an overall satisfaction with the program. Adequate clinical exposure was reported in most subspecialties except refraction and low vision rehabilitation with inadequate exposure reported by 55.8% and 95.8%, respectively. Surgical exposure was reported as adequate for phacoemulsification (58.3%) and strabismus surgery (68.3%) only. Eighty-nine percent of respondents reported performing less than 80 cases of phacoemulsification. Of the respondents who had graduated, most (89.7%) passed the final board exam at the first attempt. There were 73.5% of respondents who reported that residency training prepared them well for the board exam. Ongoing clinical and call duties were reported as having a negative impact on exam performance. CONCLUSIONS: Saudi ophthalmology residents demonstrate a high level of clinical competency. However, additional efforts should aim at improving surgical training to increase the level of satisfaction among residents and improve the quality of training to meet international standards.

Initial misdiagnosis of Vogt-Koyanagi-Harada disease.

PURPOSE: To report the initial misdiagnosis of patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: The medical records of 76 consecutive patients diagnosed with VKH disease were reviewed retrospectively at The Eye Center, Riyadh, Saudi Arabia. Patients were referred to The Eye Center from Saudi Arabia and other Middle Eastern countries. The initial diagnosis was made by an ophthalmologist or neurologist. The main outcome measure was to evaluate cases with VKH disease who were initially misdiagnosed. RESULTS: In 7 (9.2%) out of the 76 patients the initial diagnosis was incorrect. Patients were initially misdiagnosed as optic neuritis (1.3%), intracranial hypertension (1.3%), brain tumor (1.3%), Susac disease (1.3%), migraine (1.3%), rhegmatogenous retinal detachment (1.3%) or anterior granulomatous uveitis of unknown etiology (1.3%). Patients underwent unnecessary tests including MRI and invasive procedures including CSF analysis and anterior chamber paracentesis. CONCLUSION: The initial diagnosis of patients with VKH disease was incorrect in 9 % of the cases. Delay in the diagnosis of VKH disease may lead to delay in management and may cause irreversible damage to the photoreceptors with poor visual outcome.

Correction: Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.

In the original version of this article, author 'Aisha Al-Khinji' was incorrectly listed as 'Aisha Ahmed'. This has now been corrected in both the PDF and HTML versions of the article to 'Aisha Al-Khinji'.

Non-Graft-versus-Host Disease Ocular Complications after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.

Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.

Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.

Non-graft-vs.-host disease (non-GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT), but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment, and ocular toxicities associated with medications. We have summarized incidence, risk factors, screening, prevention and treatment of individual complicastions and generated evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical symptoms, signs and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplant physicians and ophthalmologists should be knowledgeable of non-GVHD ocular complications and provide comprehensive collaborative team care.

Topical tacrolimus solution in autoimmune polyglandular syndrome-1-associated keratitis.

PURPOSE: To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1. METHODS: This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy. RESULTS: A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy. CONCLUSION: Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis.

Efficacy of topical cysteamine in nephropathic cystinosis.

PURPOSE: The aim of this study is to evaluate the efficacy of topical cysteamine 0.55% eye drops in the treatment of corneal cystine crystal deposits in patients with nephropathic cystinosis. METHODS: Thirty-two patients with nephropathic cystinosis were prospectively included in the study. Patients with corneal cystinosis were treated with topical cysteamine 0.55% eye drops. They were examined before treatment, on each monthly visit and after treatment at the last follow-up. Photophobia was classified as grade 0 (none) for no photophobia, grade 1 (mild) for photophobia in bright light, grade 2 (moderate) for photophobia in room light and grade 3 (severe) for photophobia in dim light. Corneal cystine crystals were graded as grade 0=none, grade 1=1-10 crystals/mm2, grade 2=11-50 crystals/mm2, grade 3=more than 50 crystals/mm2. The main outcome measure was evaluation of photophobia and resolution of corneal cystine crystals. RESULTS: There were 13 male and 19 female patients. The mean age was 8 years with an age range of 8 months to 19 years. The mean follow-up period was 4.1 years with a range of 2-8 years. Improvement of photophobia was not clinically significant in symptomatic patients. Patients displayed statistically significant worsening of corneal cystine deposits during the follow-up period. CONCLUSIONS: This study has shown that topical 0.55% cysteamine eye drops may have limited effects in decreasing the corneal cystine deposits in patients with severe forms of nephropathic cystinosis. TRIAL REGISTRATION NUMBER: NCT02766855, Results.

Ocular findings in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease. Ocular complications occur in up to one-third of patients with SLE. The ocular findings may represent the initial manifestation of the disease and may lead to severe ocular morbidity and loss of vision. Early diagnosis and prompt management of patients with SLE are mandatory and require collaboration between the ophthalmologist and the rheumatologist.

Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of topical low-dose tacrolimus (0.01%) solution in patients with vernal keratoconjunctivitis (VKC). PATIENTS AND METHODS: A total of 62 consecutive patients with VKC refractory to conventional treatment were included retrospectively. Tacrolimus 0.01% ophthalmic solution was administered to patients twice daily after discontinuation of all previous topical medications. The duration of treatment ranged from 1 month to 29 months. The clinical symptoms of itching, redness, foreign body sensation, and discharge and the clinical signs of conjunctival hyperemia, conjunctival papillary hypertrophy, limbal infiltration, Trantas dots, and superficial punctate keratopathy were graded as 0 (normal), 1+ (mild), 2+ (moderate), or 3+ (severe). Assessment was carried out before initiation of therapy and on the last visit after treatment. RESULTS: There were 62 patients with VKC comprising 49 male and 13 female patients. The median age was 12 years (range: 5-47 years). The mean visual acuity improved from 20/30 to 20/25 following treatment. There was statistically significant improvement in symptoms of itching (P<0.001), redness (P<0.001), foreign body sensation (P<0.001), and discharge (P<0.001). Statistically significant improvement was also observed in clinical signs of conjunctival hyperemia (P<0.001), limbal infiltration (P<0.001), Trantas dots (P<0.001), superficial punctate keratopathy (P<0.001), and conjunctival papillary hypertrophy (P<0.001). The solution form of tacrolimus was well tolerated. None of the patients developed elevation of intraocular pressure, cataract, or infectious keratitis. CONCLUSION: Low-dose topical tacrolimus 0.01% solution is effective and safe in the management of patients with refractory VKC.

Associations of Systemic Diseases with Intermediate Uveitis.

PURPOSE: To determine the associations of systemic diseases with intermediate uveitis. METHODS: The medical records of 50 consecutive cases with intermediate uveitis referred to The Eye Center in Riyadh, Saudi Arabia, were reviewed. Age- and sex-matched patients without uveitis served as controls. Patients had complete ophthalmic and medical examinations. RESULTS: There were 27 male and 23 female patients. Mean age was 29 years with a range of 5-62 years. Overall, 21 cases (42%) had systemic disorders associated with intermediate uveitis and 29 cases (58%) had no associated systemic disease. A total of 11 patients (22%) had asthma, 4 (8%) had multiple sclerosis, 3 (6%) had presumed ocular tuberculosis, 1 (2%) had inflammatory bowel disease, 1 (2%) had non-Hodgkin lymphoma and 1 (2%) had sarcoidosis. Evidence of systemic disease was found in 50 (5%) of the 1,000 control subjects. Bronchial asthma was found in 37 patients (3.7 %), multiple sclerosis in 9 patients (0.9%), inflammatory bowel disease in 3 patients (0.3%), and tuberculosis in 1 patient (0.1%). None of the control patients had sarcoidosis or lymphoma. There were statistically significant associations between intermediate uveitis and bronchial asthma (p = 0.0001), multiple sclerosis (p = 0.003) and tuberculosis (p = 0.0005). CONCLUSION: Bronchial asthma and multiple sclerosis were the most frequently encountered systemic diseases associated with intermediate uveitis in our patient population. Patients with intermediate uveitis should undergo careful history-taking and investigations to rule out associated systemic illness.

Retinal artery occlusion due to Bartonella henselae infection: a case series.

PURPOSE: To report a case series of six patients suffering from branch retinal artery occlusion due to Bartonella henselae infection, in order to raise awareness to this etiology in the differential diagnosis of retinal artery occlusion. METHODS: A retrospective case series of patients with branch retinal artery occlusion due to ocular cat scratch disease who presented at four tertiary medical centers in Israel, Turkey and Saudi Arabia between the years 2008-2014. Data retrieved from the medical records included demographic data, exposure, complaints, visual acuity, clinical findings and imaging, laboratory assessment, treatment, disease course and visual outcome. RESULTS: The study group consisted of six patients who presented with branch retinal artery occlusion with or without neuroretinitis. One patient had multiple artery occlusions. Diagnosis of cat scratch disease was established based on positive serology and accompanying systemic symptoms, after ruling out other causes of retinal artery occlusion. Treatment included various regimens of antibiotics and systemic steroids. Visual outcome depended upon the obstructed artery. CONCLUSION: Cat scratch disease may cause retinal artery occlusion in infected patients, leaving them with a permanent visual field defect. When retinal artery occlusion occurs as an early sign of the disease, prompt recognition may prevent further events. Thorough history and relevant tests may be of great value.