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Alberto Mavilio,1 Dario Sisto,2 Rosanna Dammacco,2 Giuseppe Durante,1 Giovanni Alessio2 1Social Health District, Glaucoma Center, Azienda Sanitaria Locale, Brindisi, Italy; 2Department of Neurosciences, Institute of Ophthalmology, University of Bari, Bari, ItalyCorrespondence: Alberto Mavilio, Social Health District, Glaucoma Center, Azienda Sanitaria Locale, Via Napoli, 8, Brindisi, BR, 72100, Italy, Email alberto.mavilio@asl.brindisi.itPurpose: RE-PERG is altered in presence of primary neuronal degeneration of retinal ganglion cells, both in glaucoma and other diseases. A previous study showed that in a model of retrograde degeneration (vascular dementia) RE-PERG was normal. In this study, we enrolled patients with pituitary adenoma (PA) to evaluate RE-PERG findings in another model of retrograde degeneration compared with healthy controls (HC). Based on the outcome of the present and our previous studies with RE-PERG, and reviewing the literature, we discuss the physiopathology of glaucoma.Methods: Twelve PA patients and 14 age-matched HC were recruited. All participants performed visual field (VF) test, retinal nerve fiber layer (RNFL) and ganglion cells complex (GCC) thickness measurement by means of optical coherence tomography (OCT), visual evoked potentials (VEPs) and RE-PERG, a non-invasive, fast steady-state pattern electroretinogram (SS-PERG) sampled in five consecutive blocks of 130 events.Results: VEPs amplitude was significantly lower in PA with respect to HC (6.8± 0.6 vs 7.4± 0.6 μV; p=0.045). VEPs latency was higher in PA (123.2± 5.8 vs 103.6± 4.1 msec; p< 0.01). As for VF, mean defect (MD) and pattern standard deviation (PSD) were higher in PA (− 6.6± 2.6 vs − 0.01± 1.02 dB; p< 0.01 and 8.5± 3.1 vs 1.5± 0.3; p< 0.01, respectively). RNFL thickness was lower in PA (88± 8.1 vs 97± 9.3 μ; p=0.01). There was no statistically significant difference between PA and HC for RE-PERG. There was a significant correlation among MD, PSD, VEPs amplitude, PERG amplitude and RNFL thickness in the PA group, whereas no correlation was found with SDPh, which remains as normal as in the HC group.Conclusion: Our findings confirm that RE-PERG is not altered in retrograde degeneration. Based on the outcome of the present and our previous studies about RE-PERG and glaucoma, we assume that in glaucoma a double mechanism of retinal ganglion cells degeneration, both retrograde and primary, can coexist.Keywords: pattern electroretinogram, steady-state PERG, RE-PERG, visual pathway, visual field, pituitary adenoma, optical coherence tomography, visual evoked potentials

Purpose To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. Methods A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined. Results Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. Conclusion The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.

Background/Objectives: To describe frequency and type of ocular manifestations in patients with cryoglobulinemic vasculitis (CV), as well as management approaches and outcomes. Subjects/Methods: This was a retrospective, observational study of 57 patients who were diagnosed with CV at a single center and regularly underwent a comprehensive ocular assessment. Results: Ophthalmologic manifestations were recorded in 16 patients (28%). The diagnoses included dry eye disease and primary Sjögren syndrome in 5 and 2 patients, respectively; peripheral ulcerative keratitis and anterior scleritis in 1 patient each; hyperviscosity syndrome and hypertensive retinopathy in 2 patients each; and Purtscher-like retinopathy in 3 patients. Twelve patients (75%) were anti-HCV/HCV RNA-positive, 11 of whom achieved a sustained virologic response (SVR) following treatment with interferon-α2b plus ribavirin or direct-acting antivirals. All patients were treated with ocular lubricants. Systemic therapeutic measures, including glucocorticoids, immunosuppressive and biologic agents, induced the disappearance or ≥ 50% reduction of cryoglobulins and major signs of vasculitis in 11 patients (68.7%). In the remaining 5 patients (31.3%), cryoglobulins and CV manifestations remained unchanged or decreased by < 50%. The corresponding ophthalmologic assessment showed a variable degree of improvement in the ocular symptoms in all but 2 patients (87.5%). The best corrected visual acuity following treatment improved in 26 eyes, was unchanged in 3 eyes, and worsened in 3 eyes. Conclusions: Eye involvement is not a rare event in CV patients. A timely diagnosis and the correct employment of the available therapeutic measures may result in a favorable outcome of the ocular and extra-ocular manifestations.

Endogenous Endophthalmitis (EE) is a rare cause of blindness in the pediatric age group and this may account for the paucity of management guidelines in the literature. In this report, we describe our experience with a 10-year-old immunocompetent female who developed EE and became blind because of rapidly progressive and destructive inflammatory changes in her eye in spite of seemingly timely treatment.

Purpose Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate, in patients with multiple sclerosis without a history of optic neuritis (MSNON), the proportion of the different macular ganglion cell-inner plexiform layer complex (mGCIP) defect patterns. The results were compared with those of healthy controls (HCs). Methods In this cross-sectional case-control study, 34 eyes of 34 individuals, 17 with MSNON and 17 HCs, were evaluated. All participants underwent mGCIP thickness measurement using SD-OCT (Zeiss Cirrus HD-OCT 4000, macular cube protocol). The mGCIP defect patterns were classified in nine types (minimal, inner, outer, diffuse mild, diffuse severe inferior confined, inferior dominant, superior confined, and superior dominant), according to the shape derived by the deviation map of the instrument, and the proportion of each type was assessed. Results A mGCIP defect pattern was detected in 70.5% of MSNON eyes, with an inner type as the most frequent pattern (47%), followed by the outer type (11.7%) and the inferior confined type (11.7%). No defect was found in Hcs. Conclusions A significant thinning of the mGCIP with the frequent presence of an inner defect was seen in MSNON patients. The presence of this defect may serve as a biomarker of subclinical optic nerve involvement in MS patients.

We describe ophthalmic manifestations, therapy, and outcomes in 16 patients with Takayasu arteritis (TA).Takayasu retinopathy was detected in 15 eyes of 9 patients and hypertensive retinopathy in 14 eyes of 7 patients.Visual acuity was normal in 7 eyes, 20/40 to 20/200 in 20 eyes, counting fingers in 2 eyes, hand motion in 2 eyes, and no light perception in 1 eye. Glucocorticoids associated with immunosuppressive agents induced a sustained remission in 13 patients. Three relapsing-refractory patients were given the monoclonal antibody tocilizumab, which led to partial and complete response in 1 and 2 patients respectively. Steroid-induced cataracts developed in 4 patients. Restenosis and the consequent recurrence of visual symptoms were detected in 2 of 9 patients who underwent a patency procedure for their stenotic lesions.Ocular manifestations were a common feature (37.2%) in our cohort of TA patients and were frequently responsible for severe visual deterioration.BCVA: best-corrected visual acuity; FFA: fundus fluorescein angiography; GC: glucocorticoids; HR: hypertensive retinopathy; ITAS: Indian Takayasu activity score; OCT: optical coherence tomography; TA: Takayasu arteritis; TR: Takayasu retinopathy.

Purpose Giant cell arteritis (GCA), a chronic vasculitis of the large and medium-sized arteries, affects people >50 years of age. This study assessed the prevalence of visual manifestations and other clinical features at presentation in an Italian cohort of GCA patients. Recent advances in the pathophysiology, diagnosis, and therapy of GCA are also reviewed. Methods This retrospective, single-center study conducted by the ophthalmology and internal medicine clinics of one university recruited 56 patients from 2005 to 2016 and followed them for 11-54 months. Results Ocular involvement was diagnosed in 19 patients (33.9%), with permanent vision loss in 19.6% (7.1% of the cohort with bilateral vision loss). Arteritic anterior and posterior ischemic optic neuropathy were diagnosed in 11 patients (57.9%) and 1 patient (5.3%), respectively, cotton wool spots in 3 patients (15.8%), central retinal artery occlusion in 2 patients (10.5%), and anterior segment ischemia and multifocal choroidal ischemia in 1 patient each (5.3%). Polymyalgia rheumatica was associated with GCA in 44.6% of the patients. The most common extra-ocular manifestation was constitutional symptoms (82.1% of the patients). Large-vessel involvement, including of the ascending aorta, aortic arch, and left axillary artery, was diagnosed by magnetic resonance or computed tomography (CT) angiography and 18FDG positron emission/CT. Glucocorticoids (GCs) remain the standard-of-care worldwide, but methotrexate, provided as a steroid-sparing drug in 41% of the patients, resulted in earlier tapering, a lower cumulative dose of GCs, and a lower rate of relapse. Among the combinations of GCs and immunosuppressive drugs proposed to treat GCA, only tocilizumab has effectively induced and maintained disease remission. Conclusion According to our data and literature reports: a) GCA is a systemic disease; b) its diagnosis is expedited by the adjunct use of imaging techniques; c) insights into the pathogenesis of GCA may allow an improved, differentiated therapeutic approach.

Introduction This article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis. Methods This registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients' data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects. Results Since the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization. Conclusions The development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition.

Background Posterior uveitis represents the second most frequent type of uveitis (15–30% of all uveitis). Noninfectious posterior uveitis complicated with secondary cystoid macular edema (CME) affects the visual prognosis negatively. The objective of the current study is to detect possible microvascular changes causing relapsing uveitis-related CME using optical coherence tomography angiography (OCTA). Methods This is an interventional, observational, retrospective study with 1 year follow-up. Patients with noninfectious, posterior uveitis-related CME undergoing dexamethasone (DEX) implant were evaluated. Following the DEX-implant were carried out control visits after 1 month, 2-months, 4-months, 6-months, and for up 1-year. A total of 76 eyes of 38 consecutive patients with noninfectious posterior uveitis were enrolled (consecutive sample). Complicated noninfectious posterior uveitis with secondary CME was diagnosed in 56 eyes of uveitis patients (73.7%) and reviewed. Results Our investigation showed (1) a reduction in superficial vessel plexus (SVP) measurements within 2-month (84%), reaching 96.4% for up 1-year, (2) an irregular profile of SVP in 69.6% of cases, persisting for up 1-year; relapsing uveitis-related CME eyes with irregular superficial foveal avascular zone (FAZ) profile were in 51%, while the SVP measurements reestablished in 100% of cases. Conversely, (3) the deep vascular plexus (DVP) parameters restored in a lower number of eyes within the 2-month (39.3%), remaining abnormal in 46.4% of cases for up 1-year; despite DVP restored in 53.6% of cases for up 1 year, (4) a capillary rarefaction ring around the FAZ appeared in 80.4% of cases; the relapsing uveitis-related CME eyes with abnormal DVP parameters were present in 41% of cases, of which 92.1% showed a rarefaction ring had abnormal DVP. Conclusions The use of OCTA enabled the evaluation in detail of retinal microvascular changes. We suggested that the possibility of the recurrence of the uveitis-related CME depends on the persistence of modifications of the superficial and deep layers. In this regard, we propose to implement the current imaging armamentarium with OCTA for the follow-up of patients with noninfectious uveitis-related CME.

Purpose: To investigate the ocular manifestations in 91 Waldenstrom's macroglobulinemia (WM) patients.Methods: Retrospective, cross-sectional, observational analysis.Results: Ocular impairments, detected in 19 patients, included flame-shaped hemorrhages, venous sausaging, papilledema, macular detachments, or central retinal vein occlusion in 16 patients; paraproteinemic keratopathy in 2; and a CANOMAD syndrome in 1. Best-corrected visual acuity was ≥0.5 logMAR units in 11 of 38 eyes. Intraocular pressure was increased in seven eyes. Genetic analysis in seven patients showed a mutation in the MYD88 gene in six patients and a nonsense mutation in the CXCR4 gene in five patients. Plasmapheresis followed by chemotherapy with or without the addition of rituximab resulted in improvement or normalization of the ophthalmological findings in 15 patients.Conclusion: The ocular manifestations of WM are protean and potentially sight threatening. Recent advances in genomic profiling and chemotherapy have remarkably improved the hematological and ophthalmological outcomes of these patients.

Purpose To evaluate reliability of steady-state pattern electroretinogram (ssPERG) phase variability in re-test (procedure called RE-PERG) in the presence of myopia, which is known to affect ssPERG amplitude, in glaucomatous patients (GP), normal controls (NC), and myopic patients (MY). Methods The procedure was performed on 50 GP, 35 NC, and 19 MY. All subjects were examined with RE-PERG, spectral-domain coherence tomography (SD-OCT), and standard automated perimetry (SAP). Standard deviation of phase (ssPERG SDph) and mean amplitude value (ssPERG Amp) of second harmonic (2ndH) were correlated, by means of one-way ANOVA and Pearson correlation, with mean deviation (MD) and pattern standard deviation (PSD) assessed by SAP and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness assessed by SD-OCT. Receiving operating characteristics were calculated in cohort populations with and without myopia. Results GP showed significant differences from the control group for MD, PSD, RNFL, GCC, ssPERG Amp, and ssPERG SDph; GP also showed significant differences from the MY group for all the parameters except for ssPERG Amp, which is reduced in both groups. In GP group, ssPERG Amp showed a specificity of 82.1% (95% confidence interval [CI]I: 66.5-92.5). In MY group, ssPERG Amp was reduced in 58% of the patients. As a consequence of this, in GP and MY groups, considered as a whole, total specificity dropped to 70.69% (95% CI: 57.3-81.9). In the GP group, ssPERG SDph showed a specificity of 84.6% (95% CI: 69.5-91.1). In both GP and MY groups, considered as a whole, ssPERG SDph total specificity increased from 84.6% to 93.1% (95% CI: 83.3-98.1). Conclusion Intrinsic phase variability of ssPERG is not influenced by myopia, even in the presence of fundus alterations.

Purpose To describe the ocular manifestations in a cohort of patients with systemic sarcoidosis (SS). Recent advances in the pathophysiology, diagnosis, and therapy of SS are also discussed. Methods Data from 115 Italian patients diagnosed between 2005 and 2016 were retrospectively reviewed. All but the first 17 patients underwent a comprehensive ophthalmologic examination. The diagnosis was based on clinical features, the demonstration of non-caseating granulomas in biopsies from involved organs, and multiple imaging techniques. Data on broncho-alveolar lavage fluid analysis, calcemia, calciuria, serum angiotensin-converting enzyme levels and soluble interleukin-2 receptor levels were retrieved when available. Results Ocular involvement, detected in 33 patients (28.7%), was bilateral in 29 (87.9%) and the presenting feature in 13 (39.4%). Anterior uveitis was diagnosed in 12 patients (36.4%), Löfgren syndrome and uveoparotid fever in one patient each (3%), intermediate uveitis in 3 patients (9.1%), posterior uveitis in 7 (21.2%), and panuveitis in 9 (27.3%). First-line therapy consisted of corticosteroids, administered as eyedrops (10 patients), sub-Tenon’s injections (1 patient), intravitreal implants (9 patients), or systemically (23 patients). Second-line therapy consisted of steroid-sparing immunosuppressants, including methotrexate (10 patients) and azathioprine (10 patients). Based on pathogenetic indications that tumor necrosis factor (TNF)-α is a central mediator of granuloma formation, adalimumab, targeting TNF-α, was employed in 6 patients as a third-line agent for severe/refractory chronic sarcoidosis. Conclusion Uveitis of protean type, onset, duration, and course remains the most frequent ocular manifestation of SS. Diagnostic and therapeutic advancements have remarkably improved the overall visual prognosis. An ophthalmologist should be a constant component in the multidisciplinary approach to the treatment of this often challenging but intriguing disease.

Takayasu arteritis (TAK) is a rare granulomatous vasculitis of unknown etiology that mainly affects the aorta and its major branches. The aim is to describe the clinical features, diagnostic procedures, pathogenesis, and management of TAK in a longitudinal cohort of patients recruited within a single region of southern Italy. The cohort included 43 patients who were diagnosed with TAK and followed up according to a standard protocol, in a collaboration between four university tertiary referral centers and a regional hospital. Clinical and imaging classification criteria were those established by the American College of Rheumatology. Thirty-five patients (81.4%) were female, and the mean age at disease onset was 32.6 (range 16–54) years. Angiographic assessment of the vascular involvement allowed disease classification in five different types. Clinical features ranged from constitutional symptoms in the early inflammatory stage of the disease to cardiovascular ischemic symptoms in the late, chronic stage. Noninvasive imaging techniques were employed to assess the extent and severity of the arterial wall damage and to monitor the clinical course and response to therapy. Medical treatment, based on pathogenetic insights into the roles of humoral and cell-mediated immune mechanisms, included glucocorticoids mostly combined with steroid-sparing immunosuppressive agents and, in patients with relapsing/refractory disease, biologic drugs. Significant clinical and angiographic differences have been detected in TAK patients from different geographic areas. Patients with life-threatening cardiovascular and neurologic manifestations as well as sight-threatening ophthalmologic signs and symptoms should be promptly diagnosed, properly treated, and closely followed up to avoid potentially severe consequences.

Purpose To evaluate the ability of re-test pattern electroretinogram (RE-PERG), a non-invasive and fast steady-state PERG, to detect inner retinal bioelectric function anomalies in patients with early-onset Alzheimer’s disease (AD). Methods The study population consisted of 17 patients with AD-related mild cognitive impairment (MCI), 16 patients with vascular dementia (VD)-related MCI, both assessed using the neuropsychological Mini-Mental State Examination (MMSE) and by structural magnetic resonance imaging, and 19 healthy, age-matched normal controls (NC). All participants were visually asymptomatic, had normal or near-normal general cognitive functioning and no or minimal impairments in daily life activities. Visual field (VF) test, optical coherence tomography (OCT) and RE-PERG, sampled in five consecutive blocks of 130 events, were performed. Results There was no statistically significant difference among the three groups with respect to age, VF parameters (mean and pattern standard deviations) and OCT parameters (ganglion cell complex thickness and retinal nerve fiber layer thickness). The mean amplitude in the RE-PERG was significantly lower, but only weakly in the AD group than in NC (p = 0.1) whereas the intrinsic variability of the 2nd harmonic phase was significantly higher in the AD group than in either the VD or NC group (p

Purpose: To describe the ophthalmic manifestations of amyloidosis and the corresponding therapeutic measures.Methods: The 178 patients included in the study had different types of amyloidosis, diagnosed at a single internal medicine institution (Bari, Italy). To provide a comprehensive review of the types of amyloidosis that can be associated with ocular involvement, the images and clinical descriptions of patients with amyloidosis structurally related to gelsolin, keratoepithelin and lactoferrin were obtained in collaborations with the ophthalmology departments of hospitals in Mainz (Germany) and Helsinki (Finland).Results: Overall, ocular morbidity was detected in 41 of the 178 patients with amyloidosis (23%). AL amyloidosis was diagnosed in 18 patients with systemic disease, 3 with multiple myeloma, and 11 with localized amyloidosis. AA amyloidosis was detected in 2 patients with rheumatoid arthritis and 3 with Behcet syndrome, and transthyretin amyloidosis in 4 patients. The treatment of AL amyloidosis is based on chemotherapy to suppress the production of amyloidogenic L-chains and on surgical excision of orbital or conjunctival masses. AA amyloidosis is managed by targeting the underlying condition. Vitreous opacities and additional findings of ocular involvement in patients with transthyretin amyloidosis indicate the need for pars plana vitrectomy. Gelsolin amyloidosis, characterized by lattice corneal amyloidosis and polyneuropathy, results in recurrent keratitis and corneal scarring, such that keratoplasty is inevitable. In patients with lattice corneal dystrophies associated with amyloid deposits of keratoepithelin fragments, corneal transparency is compromised by deposits of congophilic material in the subepithelial layer and deep corneal stroma. Patients with established corneal opacities are treated by corneal transplantation, but the prognosis is poor because recurrent corneal deposits are possible after surgery. In patients with gelatinous drop-like dystrophy, the amyloid fibrils that accumulate beneath the corneal epithelium consist of lactoferrin and can severely impair visual acuity. Keratoplasty and its variants are performed for visual rehabilitation.Conclusion: A routine ophthalmic follow-up is recommended for all patients with established or suspected amyloidosis, independent of the biochemical type of the amyloid. Close collaboration between the ophthalmologist and the internist will facilitate a more precise diagnosis of ocular involvement in amyloidosis and allow the multidisciplinary management of these patients.Abbreviations: CD: corneal dystrophy; CLA: corneal lattice amyloidosis; CNS: central nervous system; CT: computed tomography; FAP: familial amyloidotic polyneuropathy; GDLCD: gelatinous drop-like corneal dystrophy; GLN: gelsolin; LCD: lattice corneal dystrophy; MRI: magnetic resonance imaging; OLT: orthotopic liver transplantation; TEM: transmission electron microscopy; TGFBI: transforming growth factor β induced; TTR: transthyretin.

To assess the prevalence of the ocular manifestations related to the disease and/or ascribable to the administration of potentially toxic drugs in a cohort of 98 patients with systemic lupus erythematosus (SLE).Retrospective, observational study reporting the experience of two tertiary referral centers.Overall, an ocular involvement was detected in 29 patients (29.6%), sometimes preceding of months the diagnosis of SLE, more often revealed at diagnosis or throughout its course. More than a single ocular manifestation was found in 20 of the 29 patients with ophthalmological findings (68.9%). The array of ocular morbidity included, in a decreasing order of frequency, cataracts, keratoconjunctivitis sicca, glaucoma, discoid lesions of eyelids, episcleritis, retinopathy, vortex keratopathy, choroidopathy and retinal detachment, central retinal vein occlusion, and hydroxychloroquine-induced toxic maculopathy.It is advised that a multidisciplinary team for the diagnosis and treatment of SLE should regularly include the presence of an ophthalmologist.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of undefined etiology and with remarkably heterogeneous clinical features. Virtually any organ system can be affected, including the eye. SLE-related eye involvement can be diagnosed in approximately one-third of the patients and is usually indicative of disease activity. An early diagnosis and the adoption of suitable therapeutic measures are necessary to prevent sight-threatening consequences, especially in patients with juvenile SLE. Periocular lesions, such as eyelid involvement and orbital inflammation, are relatively rare and, in case of orbital masses, may require a biopsy control. Keratoconjunctivitis sicca or secondary Sjogren’s syndrome is the most frequent ophthalmic manifestation of SLE. According to its variable severity, lubricating tear drops may be sufficient in mild cases, whereas cyclosporine-A ophthalmic solution, glucocorticoids (GCs), methotrexate, and/or other immunosuppressive drugs may be required in the more severe cases. Partial occlusion of the lacrimal punctum by thermal cautery is rarely applied. Although uncommon, episcleritis and scleritis can sometimes be detected as an initial finding of SLE and reveal themselves as moderate to intense ocular pain, redness, blurred vision, and lacrimation. Unilateral or more often bilateral retinopathy is responsible for visual loss of variable severity and is ascribed to vasculitis of the retinal capillaries and arterioles. In addition to the combined treatment suitable for all patients with active SLE, intravitreal bevacizumab should be considered in cases of severe vaso-occlusive retinopathy and laser photocoagulation in cases of neovascularization. Purtscher-like retinopathy is likely ascribable to the formation of microemboli that results in retinal vascular occlusion and microvascular infarcts. Choroidal disease is characterized by monolateral or bilateral blurred vision. Because of the choroidal effusion, retinal detachment and secondary angle-closure glaucoma may occur. Ischemic optic neuropathy is characterized by acute-onset and progressive binocular visual impairment as a consequence of occlusion of the small vessels of the optic nerves due to immune complex vasculitis. Intravenous GC boluses followed by oral GCs and/or, in case of recurrence, intravenous cyclophosphamide and/or rituximab are commonly employed. Neovascularization can be treated by intravitreal bevacizumab and progression of retinal ischemic areas by retinal laser photocoagulation. Ocular adverse events (AE) have been described following the long-term administration of one or more of the drugs presently used for the treatment of SLE patients. Posterior subcapsular cataracts and secondary open-angle glaucoma are common AE of the prolonged GC administration. The long-term administration of hydroxychloroquine (HCQ) sulfate is well known to be associated with AE, such as vortex keratopathy and in particular the often irreversible and sight-threatening maculopathy. Length of administration > 5 years, > 1000 g total HCQ consumption, > 6.5 mg/kg daily dosing, coexistence of renal disease, and preexisting maculopathy are all considered risk factors for HCQ-induced retinopathy. Ocular AE of additional immunosuppressive and biological agents are still poorly known, given the worldwide more limited experience with their long-term use. A thorough ophthalmological control is strongly recommended at closer intervals for all SLE patients, in step with the total length of exposure to the drugs and the cumulative dose administered.

Cogan’ syndrome is a multisystemic disorder characterized by the almost unfailing combination of inflammatory ocular disease and sensorineural hearing loss. In addition to constitutional symptoms, clinical features may also include cardiovascular, gastrointestinal, and neurological manifestations with variable frequency. Skin and mucous membranes, kidney and urogenital apparatus are rarely involved. The etiology remains undefined whereas an autoimmune pathogenesis is sustained by experimental and clinical observations. Given its rarity and clinical heterogeneity, the diagnosis is often delayed with possible progression to impairment of visual acuity and auditory dysfunction up to deafness. Therapy is based on the administration of glucocorticoids and immunosuppressive agents. Tumor necrosis factor-alpha blockers, the B-cell depleting monoclonal antibody rituximab, the anti-interleukin-6 receptor monoclonal antibody tocilizumab, and the immunomodulatory leflunomide have also been employed in single patients. Cochlear implantation can be used for hearing rehabilitation. Finally, stent-graft insertion and prosthetic aortic replacement can be extremely useful to correct the consequences of aortitis and large vessel aneurysms.

Purpose: Description of a patient with a solitary cyst of the pupillary margin iris pigment epithelium (IPE). Methods: A 63-year-old man referred a suspected iris-ciliary body melanoma in his left eye. Based on both clinical examination and ultrasound biomicroscopy, melanoma was considered unlikely. Surgery was under-taken to correct recurrent deterioration of vision due to movement of the lesion across the visual axis. Results: The lesion was excised completely. Ultrasound biomicroscopy and histopathological examination ruled out melanoma and allowed a final diagnosis of primary pupillary margin cyst of the IPE, characterized of pig-mented epithelium, with no connective tissue or vessels. No recurrences or fresh lesions appeared during a one-year follow-up. Conclusions: Primary epithelial iris cysts are usually benign. Treatment is required only in symptomatic patients and those with an uncertain diagnosis. Ultrasound biomicroscopy is indispensable to confirm the clinical diagnosis, follow the clinical course and intervene if surgery is required.

To evaluate the efficacy and safety of low-fluence-rate photodynamic therapy (LFPDT) to treat choroidal neovascularisation (CNV) secondary to pathological myopia (PM). Twenty-five eyes with CNV in PM underwent LFPDT, with a standard dose of verteporfin and timing but adopting fluence and irradiance rates reduced to 25 mJ/cm2 and 300 mW/cm2, respectively. Best corrected visual acuity (BCVA) was measured and biomicroscopy and fluorescein angiography (FA) were evaluated. Particular attention was paid to choroidal hypoperfusion, and to changes (depigmentation/atrophy) at the RPE level in areas exposed to laser light. After a mean follow-up of 13.4 ± 2.46 months (range: 12–21), and 1.37 ± 0.66 treatments (range: 1–3), BCVA was stable in 29 (91%) eyes. Two (6%) patients gained more than three lines and one (3%) eye lost more than three lines. Mean greatest linear dimension did not change significantly (p = 0.08) at the end of follow-up. RPE depigmentation was present in six eyes (18%) and no patient showed RPE atrophy. LFPDT is effective and safe for CNV secondary to PM treatment, stabilizing visual acuity and lesion size and determining only mild RPE changes. Further controlled studies are needed to demonstrate the long-term efficacy and safety of this treatment option.

Orbital pseudotumor is a benign, idiopathic, non-infectious and non-neoplastic clinical syndrome characterized by the presence of an inflammatory mass at orbital level with no identifiable cause. The disease is rarely observed in the pediatric population. This article describes a relapsing bilateral orbital pseudotumor in a young girl. The diagnostic implications and treatment strategies are discussed.

Purpose: To describe a case of localized Kaposi sarcoma (KS) of the eyelid in an HIV-seronegative patient. Methods: An 80-year-old man developed an ulcerated nodular tumor-like mass that grew rapidly on his left upper eyelid. There were no similar lesions elsewhere. The eyelid lesion was completely excised and histopathologically examined. Serological analyses and molecular biologic techniques, including polymerase chain reaction, were used. Results: Laboratory examinations were within normal limits, and serology for HIV was negative. Histological sections revealed a vascular proliferation composed predominantly of small slit-like blood vessels and epithelioid spindle cells, supporting the diagnosis of KS. Polymerase chain reaction was positive for human herpesvirus 8. During a 2-year follow-up, no recurrences, development of new lesions, or HIV seroconversions were observed. Conclusion: This is a classic KS involving only the eyelid in an HIV-negative patient. Location in the eyelid is a possible, albeit rare, initial solitary manifestation of KS in elderly HIV-negative patients. Surgery is both safe and effective.

To evaluate safety and efficacy of intravitreal triamcinolone acetonide (TAAC) injections in the treatment of refractory pseudophakic cystoid macular edema (CME).Seven eyes of six patients (age range: 50-74) with pseudophakic CME resistant to standard treatment received intravitreal injections of 4 mg of TAAC with all vehicle. Mean preinjection duration of CME was 18.3 months. A mean of 2.1+/-1.2 (range 1 to 4) treatments were performed in four eyes (57.1 %) when visual acuity deteriorated towards baseline levels. Visual acuity assessment, optical coherence tomography (OCT), and fluorescein angiography (FFA) were performed pre- and postoperatively to evaluate results of TAAC injections. Intraocular pressure (IOP) and complications related to treatment were assessed.After 11.1+/-3.9 months, mean best-corrected visual acuity (BCVA) increased (p =0.019) from 20/132 to a best value of 20/38. Mean macular thickness decreased from 517.29+/-146.98 mm to a best value of 263.71+/-83.13 mm (p=0.0018). Area of fluorescein leakage decreased (p0.0001) from 11.84+/-0.93 mm2 at baseline to a minimal value of 3.86+/-0.98 mm2. The anatomic and functional improvement appeared after 1 month from the intravitreal injection and persisted through at least 3 months of follow-up. At the end of follow-up BCVA, macular thickness, and area of fluorescein leakage did not differ from baseline. Four eyes (57.1 %) developed IOP values higher than 21 mmHg, controlled by topical treatment. Two patients developed an endophthalmitis-like reaction.Intravitreal TAAC was relatively safe and effective in resistant cases of pseudophakic CME with a temporary beneficial effect on visual acuity and macular edema.

Background The aim of this study was to identify the main features of a cohort of Caucasian patients with idiopathic (I) and systemic disease-associated (SDA) autoimmune uveitis (AU) who were followed up at a single tertiary reference center. The study consisted of a retrospective analysis of the demographic, clinical, and laboratory features and the response to treatment of 104 patients with AU evaluated between 2004 and 2013, with a median follow-up of 4.8 years. The primary outcome measure was the response to systemic treatment after 24 months of therapy. The data are expressed as the range, percentage, or mean ± standard error. Categorical variables were assessed by Fisher's exact test. Results The mean age at diagnosis was 40.1 ± 17.8 years for men and 44.1 ± 15.3 years for women. There was a slight female predominance. Of the 104 patients, 72.1% had I-AU and 27.9% SDA-AU. The most frequent associations were with ankylosing spondyloarthritis, autoimmune thyroiditis, inflammatory bowel diseases, and Behcet's disease. Symptoms at presentation consisted of eye redness and pain (28.8%), decreased visual acuity (25.9%), and floaters (18.3%). Complications included cataracts (24%), retinal neovascularization (16.3%), chorio-retinal scars (10.6%), cystoid macular edema (8.6%), glaucoma/ocular hypertension (7.7%), epiretinal membranes (4.8%), and retinal detachment (3.8%). The prevalence of autoantibodies, mostly antinuclear antibodies, was comparable between the I-AU and SDA-AU groups. Fisher's exact test showed a direct correlation between patients with class I HLA B27, Cw8, B5 (51, 52), B51, or Cw2 and the presence of AU, whereas among patients with class II HLA, only DQ1 was a predisposing factor for AU. The therapeutic spectrum included corticosteroids and immunosuppressive agents, given either alone or in various combinations according to the severity of AU and the extent of the clinical response. Among the immunosuppressive drugs, azathioprine was preferentially used for anterior uveitis, and cyclosporine-A for intermediate and posterior uveitis. An assessment of the patients after 24 months of therapy showed a complete remission in 43.3% and a significant clinical improvement in 26.9%. Conclusions At our tertiary reference center, the prevalence in Caucasian patients of I-AU was approximately 2.5-fold higher than that of SDA-AU. Our findings point to the need for a patient-tailored therapeutic approach according to the anatomic site and the severity of AU. Therapy should be prolonged, over a period of months and even up to 1–2 years, in order to achieve stable control of the disease and to prevent severe complications. The outcome of SDA-AU is also influenced by treatment of the underlying systemic disease. Additional controlled trials are needed to assess the efficacy and the long-term safety of both the prescribed therapeutic agents and their combinations.

Objective. To investigate whether immunologic abnormalities in patients with Behcet's disease (BD) are related to abnormalities of the Th1/Th2 ratio. Methods. Th1/Th2 cytokine production by peri- pheral blood lymphocytes (PBL) from 31 patients with BD, 11 patients with inflammatory arthritis, and 10 healthy blood donors was evaluated by intracellular immunofluorescence staining. Serum interleukin-12 (IL-12) levels were measured using an enzyme amplified-sensitivity immunoassay. The effect of recom- binant IL-12 (rIL-12) on spontaneous and Fas-mediated apoptosis of phytohemagglutinin (PHA)-stimulated PBL was evaluated by flow cytometry using propidium iodide (PI) staining and a bromodeoxyuridine (BrdU)/PI procedure. Results. Intracellular immunofluorescence staining of IL-2, IL-4, and interferon-g (IFNg )i n CD31 lympho- cytes from BD patients demonstrated a strong polarization of the immune response toward the Th1 pathway that correlated with the progression of BD. Peripheral Th1 cells were significantly increased in patients with active disease (n 5 14) as compared with those in patients in complete remission (n 5 17), patients with inflammatory arthritis, and normal donors. In addition, serum IL-12 levels were correlated with peripheral Th1 lymphocytes and disease progression. Apoptotic analysis revealed that PHA- activated PBL from patients with active disease were highly sensitive to spontaneous and Fas-mediated activation-induced cell death. However, addition of rIL-12 to complete medium prevented this spontaneous and Fas- induced apoptosis and enhanced the proliferation of Th1 lymphocytes. Conclusion. Taken together, these results indicate that a strong Th1 immune response occurs in active BD and suggest that IL-12 plays a substantial part in the pathogenesis of BD. By preventing spontaneous and Fas-induced cell death, in fact, it results in an abnormal growth of autoreactive Th1 lymphocytes that could contribute to the prolonged inflammatory autoimmune condition of BD.

Purpose Epiretinal membranes (ERM) are a common finding in old patients. Pars plana vitrectomy is effective for removing ERM from the macula, but some postoperative complications are relatively frequent. In the present report, we describe a 73-year-old man in whom extrafoveal choroidal neovascularization developed four months after surgery. Methods Choroidal neovascularization was treated by argon laser photocoagulation. Results: Six months after treatment, the choroidal neovascularization was obliterated, with no recurrence of ERM. Conclusions Choroidal neovascularization can be an unusual complication of ERM surgery, and should be suspected in case of poor visual outcome or recurrence of symptoms.

PURPOSE Aggressive posterior retinopathy of prematurity (APROP) may suddenly develop into tractional retinal detachment (TRD), often resulting in poor vision if untreated. The aim of the current study is to examine the anatomic results and complications of lens-sparing vitrectomy (LSV) for stage 3 APROP, before TRD appearance. METHODS A retrospective, noncomparative, consecutive case series of 13 eyes of 9 patients (mean gestational age 24.1+/-0.9 weeks [range: 23-25 weeks], mean birthweight of 725.8+/-107.9 grams [range: 598-897 grams]) with stage 3 APROP was carried out. The eyes did not respond to at least one session of retinal laser photocoagulation, showing signs of disease progression. All eyes underwent 20-gauge LSV before retinal detachment appearance. RESULTS All eyes underwent 20-gauge three-port LSV and intraoperative additional laser photocoagulation. At the end of the surgery, five eyes were tamponaded with air; in eight eyes, a balanced salt solution was left in the vitreous cavity. After 13.5+/-5.3 months of follow-up (range: 4-22), the retina was completely attached in all eyes, without any signs of progression. The authors did not observe any intraoperative or postoperative complications. CONCLUSIONS Surgical approach to stage 3 APROP refractory to laser photocoagulation could be effective and safe in order to avoid the progression of the disease.