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Purpose: To describe the clinical and molecular implications of a novel mutation in the NOD2/CARD15 gene on a family and its seven affected members.Methods: We reviewed the clinical presentations of family members who came to our center for refractory uveitis. Genetic testing and molecular testing was performed.Results: All affected members had adult onset recurrent non-granulomatous panuveitis. The inheritance pattern suggested an autosomal dominant disease and genetic analysis identified a novel mutation in the NOD2 gene that converted amino acid 600 from glutamate to alanine (E600A). Transfection of the E600A NOD2 into human embryonic kidney-293 (HEK293) cells revealed constitutive activation and a reduced ability to respond to the NOD2 ligand, muramyl dipeptide (MDP) as compared with wild-type NOD2.Conclusions: The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement.

To describe the clinical and visual outcomes of juvenile idiopathic arthritis (JIA)-associated uveitis in adults and to examine risk factors for ongoing inflammation in adulthood. Medical records were reviewed for patients with JIA-associated uveitis who were >16 years old at the final visit (the last visit prior to data collection). In total, 135 eyes of 77 patients (70 female, 7 male) were included. The mean age of patients at the final visit was 29.72 ± 11.27 years. The number of eyes with visual acuity of ≤20/50 and ≤20/200 at the final visit was 37 (28 %) and 20 (15 %), respectively; at least one ocular complication was present in 72 % of eyes. Band keratopathy was the most frequent complication (42 %), followed by cataract (25 %), posterior synechiae (22 %), maculopathy (22 %), ocular hypertension (13 %), and hypotony (5 %). At the final visit, patients who were >16 years of age at presentation to the Massachusetts Eye Research and Surgery Institution had more ocular complications and a greater degree of vision loss than patients who were ≤16 years of age. Ongoing inflammation at the final visit was noted in 40 patients (52 %). The presence of posterior synechiae, hypotony, cataract at presentation, and a history of cataract surgery prior to presentation were predictive of ongoing inflammation in adulthood in univariate analysis. The presence of hypotony and posterior synechiae at the initial visit were predictive factors in multivariate analysis. JIA-associated uveitis may be associated with ongoing inflammation, ocular complications, and severe visual impairment in adulthood. The presence of posterior synechiae and hypotony at the initial visit is predictive of ongoing inflammation.

Juvenile idiopathic arthritis (JIA) is the most common childhood systemic disease associated with uveitis and significantly detracts from the child’s quality of life. Due to the high rate of ocular morbidities in JIA associated uveitis, the main treatment goal remains the complete elimination of active inflammation at all times. An aggressive ‘step-ladder’ approach starting with conventional immunotherapy is usually tried initially in order to control the ocular inflammation. For those who fail conventional therapy, biologic response modifiers have been shown to be effective in controlling the inflammation. Available data demonstrate the extensive and successful, yet off-label, use of biologic agents in the treatment of refractory JIA associated uveitis especially in cases that fail or deemed intolerant to conventional immunosuppressive therapy. In this review, we discuss different biologic response modifiers; their applications in the treatment of JIA associated uveitis and their safety profile i...

Uveitis is a common and serious complication of juvenile idiopathic arthritis. Up to 75% of all cases of anterior uveitis in childhood are associated with juvenile idiopathic arthritis. Despite the remarkable progress in early detection and treatment of inflammation, vision-threatening complications of uveitis still occur in almost 60% of patients. Structural complications include band keratopathy, maculopathy (macular edema, macular cysts, and epiretinal membrane), glaucomatous optic neuropathy, and cataracts. The management of complications in juvenile idiopathic arthritis is usually complex and requires early surgical intervention. In this paper, we review the general concepts of common ocular complications seen in patients with JIA-associated uveitis, with special attention to the recent diagnostic and preferred treatment approaches at the Massachusetts Eye Research and Surgery Institution. Received 9 March 2015; revised 30 September 2015; accepted 30 October 2015; published online 14 January 2016.

Purpose Drug-induced uveitis is a well-known effect of ocular inflammation that has been reported with many medications. Pembrolizumab is a newer generation of the anti-programmed cell death-1 monoclonal antibodies that was recently approved by the Food and Drug Administration for the treatment of advanced melanoma. Immune-mediated adverse events involving different organs have been reported in recent literature in association with this drug. We present the first reported case of uveitis in association with pembrolizumab therapy. Case report An 82-year-old man with stage IV melanoma was started on pembrolizumab infusion treatment every 3 weeks. Two months after initiating therapy, he presented with bilateral severe anterior uveitis and papillitis with fast and complete recovery after withholding further pembrolizumab infusions and treatment with topical steroid. Uveitis recurred after restarting pembrolizumab therapy. Conclusions In current clinical practice, many new drugs are being approved, requiring better characterization of the prevalence, onset, and nature of adverse events in order to aid development of effective management strategies. Ophthalmologists should keep in mind that drugs are always a possible cause of ocular inflammation in patients presenting with uveitis.

Purpose: To describe clinical manifestations, diagnostic approaches, therapy, and outcomes of biopsy-proven intraocular lymphoma.Methods: Review of tertiary referral center records between 2005 and 2015.Results: A total of 51 eyes of 26 patients were included; mean age of onset was 60.42 years. Common ocular complaints included floaters (42%) and blurred vision (35%); 62% of patients had ocular and central nervous system involvement; 11% had systemic lymphoma; and 27% had only ocular involvement. Vitreous analysis was positive for malignant cells in 77% of patients on initial biopsy, and in 100% of patients on repeat biopsy. In total, 20/26 patients received systemic and topical treatment before IOL diagnosis was made; 25 patients received intravitreal methotrexate and/or rituximab; one patient received intracameral rituximab. All patients achieved remission by their final visit.Conclusions: Intraocular lymphoma often masquerades as intraocular inflammation, resulting in delayed or misdiagnosis with subsequent inappropriate management. Optimal therapy is a challenge for oncologists and ophthalmologists.

Granulomatosis with polyangiitis (GPA) is a potentially lethal systemic disorder that is characterized by necrotizing vasculitis of small arteries and veins. The respiratory system is most commonly affected in limited forms of the disease, however upper and lower respiratory system, systemic vasculitis, and necrotizing glomerulonephritis are the characteristic components of the disease triad. The peak incidence is observed at 64-75 years of age, with a prevalence of 8-10 per million depending on geographic location. In this review we focus on the ocular manifestations of the disease which occur in nearly in one third of the patients. In addition we describe the neuro-ophthalmic complications which occur in up to half of cases. We also discuss the current systemic treatment options including corticosteroids, cyclophosphamide, azathioprine, and the available biologic response modifiers including rituximab. The disease remains difficult to diagnose due to the generalized symptomatic presentation of patients with GPA. As a result, several sets of diagnostic criteria have been developed which include clinical, serological, and histopathological findings to varying extents. Early diagnosis and multi-specialty collaboration among physicians is necessary to adequately manage the disease and the potential complications that may result from drugs used in the treatment of the disease. Despite recent advances, more research is necessary to prevent the high rates of mortality from the disease itself and from therapeutic side effects.

Introduction: Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

Head trauma is a major medical, social, economic, national, and public health priority issue in the United States. In severe head trauma, the overwhelming clinical manifestations are so compelling that damage to the visual system is most likely to be ignored. Both the afferent and efferent visual systems are susceptible to injury after head trauma, and physicians should be aware of the visual system and perform a thorough neuro-ophthalmic evaluation in patients presenting with head trauma.Most of the data available on neuro-ophthalmic complications of head trauma including cortical blindness, Horner's syndrome, traumatic internuclear ophthalmoplegia, and ocular motor palsy, comes from case reports highlighting the need for future studies to better understand these complications.This review summarizes some of the most important neuro-ophthalmic complications of head trauma including cortical blindness, Horner's syndrome, traumatic internuclear ophthalmoplegia, and ocular motor palsy. Search of the peer-reviewed literature was conducted using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult.

The preeclampsia/eclampsia syndrome is a multisystem disorder that can include cardiovascular changes, hematologic abnormalities, hepatic and renal impairment, and neurologic or cerebral manifestations. It also can affect the eye and visual pathways. Visual symptoms concern up to 25% of patients with severe preeclampsia and 50% of patients with eclampsia. This review discusses the ophthalmic complications of preeclampsia/eclampsia with focus on the hypertensive retinopathy, exudative retinal detachment and cortical blindness.

Purpose: This study aimed to estimate the prevalence of pseudoexfoliation syndrome (PXS) and analyse its association with particular ocular diseases in patients attending the Department of Ophthalmology at Jordan University Hospital. Methods: A total of 1195 consecutive patients, aged 40–90 years, who attended the Department of Ophthalmology at Jordan University Hospital between December 2005 and March 2007 were included in the study. Each patient underwent complete ophthalmic evaluation, including: relevant history; visual acuity testing; slit-lamp examination, applanation tonometry, gonioscopy and dilated fundus examination. Patients with typical pseudoexfoliative material on the anterior lens surface and/or the pupillary margin in either or both eyes were labelled as having PXS. Results: Of the 1195 patients, 9.1% had pseudoexfoliation (PXF). Their mean age was 68.3 years (standard deviation [SD] 9.57). The prevalence of PXS had a tendency to increase with age but had no sex predilection. Pseudoexfoliation was bilateral in 65.7% of cases. It was significantly associated with cataract, glaucoma and phacodenesis. Of the eyes with PXF, 92.1% had cataract, 33.1% had glaucoma and 7.9% had phacodenesis. Conclusions: Although this study was not population-based, its findings increase our knowledge of PXS in a Middle Eastern country. Few data on PXS are available from this part of the world.

Introduction Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (ViagraR), tadalafil (CialisR), and vardenafil (LevitraR) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3–11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. Aims To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. Methods Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. Main Outcome Measures To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. Results Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. Conclusion There is lack of conclusive evidence to indicate a direct cause–effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3–11% of users and they are transient and reversible.

Ocular complications of sexually transmitted diseases are frequently encountered by ophthalmologists and sexual health physicians in everyday practice. Ocular findings may be the first sign of many of the known sexually transmitted diseases. Thus, a high index of suspicion for ocular involvement in patients at risk of sexually transmitted diseases should be borne in mind and these patients should be referred to a specialist in a timely manner. This review focuses on the more significant ocular manifestations of the most common sexually transmitted diseases with which both ophthalmologists and sexual health physicians need to be familiar. In addition, it provides the most recent statistics on these conditions.