Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role.

BACKGROUND: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. PURPOSE: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. METHODS: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. RESULTS: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. CONCLUSION: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

Familial Mediterranean fever associated frosted branch angiitis, retinal vasculitis and vascular occlusion.

OBJECTIVES: To analyse the entity of retinal vasculitis, including frosted branch angiitis (FBA), or retina vascular occlusion in patients with familial Mediterranean fever (FMF). METHODS: Retrospective collaborative case series using invitation by email to uveitis specialists around the Mediterranean basin. This series was combined with a literature review. Exclusion criteria included infectious diseases, Behçet's disease or other autoimmune diseases. RESULTS: A total of 16 patients (21 eyes) had FMF and retinal vasculitis (FBA 11 patients, mild retinal vasculitis 5 patients). The mean age at onset of vasculitis was 29.5 ± 13.4 (range 9-62) with a female to male ratio of 9 to 7. In 19 eyes treated with various forms of corticosteroid and/or immunosuppression, the mean initial spectacle-corrected visual acuity improved from 6/194 to 6/10.5 at the last mean follow-up of 29.0 ± 34.9 months (p < 0.001). The most common FEVR mutations were M680I and M694V. In addition, retinal vascular occlusions included one case of central retinal artery occlusion and one case of branch retinal artery occlusion. CONCLUSION: FBA and milder forms of retinal vasculitis are associated with FMF. Therapy involves an increase in colchicine dosage in early cases, a long period of oral corticosteroid, intravitreal dexamethasone implant or periocular corticosteroid in select cases, and combination therapy with systemic immunosuppression in severe cases. FMF needs to be included in the differential diagnosis of retinal vasculitis.

Platelet Activation in Ocular Behçet's Patients with Posterior Segment Involvement.

PURPOSE: The aim of the present study was to assess platelet activation by analyzing three platelet activation parameters in ocular Behçet's disease (BD): mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT). METHODS: Twenty-nine patients with active ocular BD (Group 1), 40 patients with inactive ocular BD (Group 2), and 40 healthy adult individuals serving as controls (Group 3) were evaluated. All of the individuals had been performed the complete ophthalmologic evaluation. The levels of MPV, PDW, and PCT were measured in each group. RESULTS: The mean MPV level was 8.40 ± 0.97 in Group 1, 8.32 ± 1.04 in Group 2, and 7.77 ± 0.72 in Group 3. The mean PDW level was 15.12 ± 1.09 in Group 1, 14.97 ± 1.02 in Group 2, and 14.52 ± 0.82 in Group 3. The mean PCT level was 0.23 ± 0.07 in Group 1, 0.21 ± 0.04 in Group 2, and 0.18 ± 0.03 in Group 3. MPV, PDW, and PCT levels were significantly higher in ocular BD patients than controls (P < 0.05). CONCLUSION: Platelet activation may affect vascular occlusion in ocular Behçet's patients with posterior segment involvement. This result may be important in evaluating ocular BD patients.

Demographic and Clinical Characteristics of Uveitis in Turkey: The First National Registry Report.

PURPOSE: To describe the demographic and clinical profiles of uveitis patients seen at secondary and tertiary care centers in Turkey. METHODS: A nationwide web-based registry of patients with uveitis was initiated in November 2008. We analyzed data from a single baseline registry-enrollment visit. RESULTS: In 33 centers, 6967 eyes of 4863 consecutive patients were registered. The mean age at presentation was 36.6 ± 15.7 (1-92) years; 51.3% were male. Behçet disease was the leading diagnosis (24.9%), followed by ankylosing spondylitis and/or HLA-B27-associated anterior uveitis (9.7%), toxoplasmosis (7.1%), Fuchs uveitis (6.3%), and presumed herpetic anterior uveitis (6.0%). Visual acuity was 0.1 or worse in 22% of eyes. The most common ocular complications were posterior synechiae (16.2%) and cataract formation (16.2%). CONCLUSIONS: Behçet disease is still the most common non-infectious etiology in Turkish uveitis patients, while ocular toxoplasmosis and herpetic anterior uveitis are the most common infectious uveitic entities.

Increased levels of circulating CD34+ cells in neovascular age-related macular degeneration: relation with clinical and OCT features.

PURPOSE: To investigate the levels of circulating CD34+ stem cells in patients with neovascular type age-related macular degeneration (AMD) and its relation with clinical and optical coherence tomography (OCT) findings. METHODS: The study consisted of 55 patients: 28 patients (18 male and 10 female) with neovascular type AMD as a study group and 27 patients (12 male and 15 female) scheduled for cataract surgery as a control group. The level of CD34+ stem cells was measured by flow cytometry. Demographic and clinical data were recorded. RESULTS: The mean ages of patients in the study and control groups were 71 ± 8 and 68 ± 6 years, respectively. There was no statistically significant difference in terms of age, sex, or systemic disease association between study and control groups. However, smoking status was significantly higher in the study group (67.9% vs 37.0%; p = 0.02). Stem cell levels were significantly higher in the study group (1.5 ± 0.9 vs 0.5 ± 0.3; p<0.001), but there was no relation between stem cell levels and clinical and OCT findings. CONCLUSIONS: Increased circulating CD34+ stem cell levels were observed in patients with choroidal neovascular membrane associated with AMD, but no significant relation was found between cell levels and clinical and OCT findings.

Clinical and Demographic Characteristics of Patients with Uveitis Starting Later in Life.

PURPOSE: To evaluate uveitis cases presenting at older ages for the first time. METHODS: We retrospectively analyzed the clinical data related to the 90 eyes of 68 patients who presented with a first episode of uveitis at the age of ≥60 years and were seen at the Uveitis Division of the Ulucanlar Eye Hospital from 1996 to 2013. RESULTS: The location of the uveitis was anterior in 51 (75%) patients. Nine patients (13.2%) presented with panuveitis, 5 (7.3%) with posterior uveitis, and 3 (4.4%) patients with intermediate uveitis. Idiopathic uveitis in 23 (33.8%) and presumed herpetic anterior uveitis in 23 (33.8%) patients were the most common diagnoses, while other diagnostic entities accounted for 22 (32.3%) patients. The most common complications were elevation of intraocular pressure in 17.7%, cystoid macular edema (CME) in 11.1%, and corneal scar in 11.1% of eyes. CONCLUSIONS: While idiopathic uveitis and presumed herpetic anterior uveitis were the most common causes, although in an endemic country, Behçet disease was not a common cause of uveitis in the elderly population.

Presumed herpetic anterior uveitis: a study with retrospective analysis of 79 cases.

PURPOSE: To describe the clinical features, visual outcome, medical treatment, and complications of presumed herpetic anterior uveitis. METHODS: We retrospectively analyzed the clinical data related to 79 eyes of 77 patients with presumed herpetic anterior uveitis seen at the Uveitis Unit of the Ulucanlar Eye Training and Research Hospital from 1996 to 2011. Age at onset of disease, sex, follow-up duration, existence of corneal involvement, posterior synechiae, distorted pupil, iris atrophy, characteristic of keratic precipitates, elevated intraocular pressure (IOP), medical treatment, recurrence rate, complications, visual acuities (VA), and surgery for complications were recorded. The complication rates in patients with and without corneal involvement were compared. RESULTS: There were 38 (49.4%) female and 39 (50.6%) male patients. The mean age at presentation was 48.5 ± 14.8 (20-82) years. The follow-up period was 26.5 (2-127) months. Two patients had bilateral involvement. Ocular findings were a corneal scar or active keratitis in 37 (46.8%) eyes, secondary glaucoma in 14 (17.7%), iris atrophy in 39 (49.4%), distorted pupil in 16 (20.3%), posterior synechiae in 23 (29.1%), and granulomatous anterior uveitis in 30 (40%) eyes. Eight (10.1%) eyes had a posterior subcapsular cataract. Glaucoma surgery was required for uncontrolled IOP with maximum medical treatment in 2 (2.4%) eyes. Long-term oral acyclovir was used in 9 (11.3%) patients. Final VA was ≤ 0.1 in 8 (10.1%) eyes; of these, 6 had either corneal scarring or cataract and 2 preexisting amblyopia. CONCLUSIONS: Presumed herpetic anterior uveitis with or without keratitis has characteristic clinical findings that enable the diagnosis. Long-term prophylactic antiviral therapy should be considered especially in patients <50 years old.

Congenital simple hamartoma of retinal pigment epithelium: clinical and imaging findings.

Congenital simple hamartoma of retinal pigment epithelium (CSHRPE) is a rare, asymptomatic, and incidentally detected benign lesion. However, it is very important to do the differential diagnosis from other pigmented retinal lesions. Its clinical presentation and imaging findings are very helpful in doing this differentiation. This paper presents clinical and imaging findings of a 56-year-old woman with incidentally detected CSHRPE. The lesion was small, heavily pigmented, well circumscribed, and slightly elevated. Optical coherence tomography (OCT) scanning was diagnostic and showed an elevated retina at the site of the lesion, increased optical reflectivity on its inner surface, optical shadowing of deeper structures, and clearly cut tumor margins. Ocular ultrasonography, fluorescein angiography, and fundus autofluorescence imaging which is firstly described in this report did not show any characteristic finding.

Patterns of childhood-onset uveitis in a referral center in Turkey.

PURPOSE: This study aimed to investigate the frequency and characteristics of childhood-onset uveitis and evaluate the rate and specific causes of visual loss in this population. METHODS: The data of 121 patients (179 eyes) with uveitis starting before ≤16 years and followed up for at least 6 months were retrospectively evaluated. Age at onset, sex, laterality, associated systemic disease, laboratory data, therapeutic strategies, surgeries, final visual acuity, and causes leading to visual acuity ≤20/200 were analyzed. RESULTS: Childhood-onset uveitis made up 9.6% of our uveitis patients. The mean age at onset was 11.7 years (1-16) and the mean follow-up period was 38.5 months (6-148). Forty-three patients (35.5%) were female and 78 were male (64.5%). The disease was bilateral in 58 (47.9%) and unilateral in 63 (52.1%) patients. Uveitis was mostly (59.5%) seen between 12 and 16 years of age. Pars planitis, observed in 29 (24%) patients, was the leading cause of childhood-onset uveitis. Uveitis was idiopathic in 20 (16.5%) of patients. The most frequently associated diseases were Behcet's disease (BD) in 20 (16.5%), toxoplasmosis in 16 (13.2%), and juvenile idiopathic arthritis (JIA) in 8 (6.6%) patients. Anterior uveitis was observed in 38 (31.4%), intermediate uveitis in 31 (25.6%), posterior uveitis in 30 (24.8%), and panuveitis in 22 (18.2%) patients. The final visual acuity was ≤20/200 in 32/179 eyes (17.9%) of 27/121 patients (22.3%). The most often ocular complication leading to visual acuity ≤20/200 was optic atrophy and had been observed in 14 of 32 eyes (43.7%). Macular scar observed in five eyes (15.6%) was the second most often complication. Etiological distribution of 27 patients with visual acuity ≤20/200 was as follows: 12 had BD (44.4%), 5 had idiopathic uveitis (18.5%), 4 had pars planitis (14.8%), 3 had toxoplasmosis (11.1%), 2 had JIA (7.4%), and 1 had toxocara (3.7%). CONCLUSIONS: Although rare, childhood-onset uveitis has a blinding potential and causes visual loss in up to 22.3% of the patients. In endemic areas like Turkey, BD may be the most common uveitis-associated systemic disease and the leading cause of visual loss in childhood uveitis as adulthood.

Cyclooxygenase-2 expression in human irradiated uveal melanomas.

AIM: Previous studies have shown that radiotherapy is a stimulus for cyclooxygenase-2 (COX-2) expression and that use of COX-2 inhibitors enhances the radio sensitivity of tumor cells. The objective of this study was to evaluate COX-2 expression, and its correlation with tumor regrowth after irradiation, in enucleated eyes with uveal melanomas. METHODS: Fifteen tissue samples from patients who underwent enucleation after radiotherapy between 1988 and 2001 were used. Nine cases (60%) were enucleated because of tumor regrowth and six (40%) because of severe complications of radiotherapy. Specimens were immunostained for COX-2, and tumor cells were evaluated for specific cytoplasmic and granular immunostaining. COX-2 expression for these cases was compared with that in the previous study including 40 non-irradiated uveal melanoma cases. COX-2 expression was also correlated with tumor regrowth after radiotherapy. RESULTS: Two cases (13.3%) were positive and thirteen (86.7%) were negative for COX-2 expression. One of the positive cases had been enucleated because of tumor regrowth and one because of radiotherapy complications. There was no relationship between tumor regrowth and COX-2 expression. COX-2 expression was significantly lower in irradiated cases than in non-irradiated cases in the previous study (p<0.001). CONCLUSIONS: In contrast with studies showing an increase of COX-2 expression in other irradiated malignancies, irradiation was not a factor inducing COX-2 in uveal melanomas. Radiotherapy may, moreover, be a factor that reduces COX-2 expression in uveal melanomas.

Combination of azathioprine and corticosteroids in the treatment of serpiginous choroiditis.

BACKGROUND: Although therapy with immunosuppressive agents is currently accepted as the best option for treating active serpiginous choroiditis (SC), there is no consensus on the most effective immunosuppressive drug to use. In this paper, we describe the clinical course of patients with active SC treated with azathioprine (AZA) in combination with corticosteroids. METHODS: This retrospective study included 4 patients (5 eyes) with active, vision-threatening SC who received systemic immunosuppression with AZA at 1.5 to 2.0 mg/kg per day. In combination with oral AZA, patients also received 1 mg/kg oral prednisone per day. Information collected included Snellen visual acuity (VA), clinical disease activity, duration of follow-up, rate of inflammation recurrence, and side effects of AZA. RESULTS: Within 3 weeks of treatment, all patients experienced decreased ocular inflammation and improved VA. One patient, however, had a recurrence in both eyes while oral prednisone was being tapered. In this case, once the dosage of oral prednisone was increased and methotrexate was added to the therapeutic scheme, inflammation was controlled within 1 month. The other 3 patients presented no further visual loss while on AZA and were able to taper and then discontinue oral prednisone. Nevertheless, SC recurred in 1 of these patients 40 months after the initial treatment. AZA was reintroduced but the patient complained of gastrointestinal problems, and it was then successfully replaced by mycophenolate mofetil. None of the 4 patients presented serious systemic side effects secondary to AZA. INTERPRETATION: This study suggests that when AZA is used in combination with corticosteroids it is a safe and acceptable option for treating patients with active SC. Side effects and recurrences while on AZA therapy can occur, requiring either replacement of the drug or addition of another immunosuppressive agent.

Chemoattraction of inflammatory cells by various intraocular lens materials.

PURPOSE: To compare the chemotactic activity induced by polymethyl methacrylate (PMMA), acrylic, and silicone intraocular lens (IOL) materials, regardless of the surgical and host factors. METHODS: The chemotactic effect of five different IOLs was studied using a modified multi-well Boyden chamber. Two different non-coated PMMA IOLs, a heparin-coated PMMA IOL, an acrylic IOL, and a silicone IOL were assessed. Each mean migration distance of the IOLs was compared with the others using Student's t test. RESULTS: All IOLs induced some amount of leukocyte chemotaxis. There was no statistically significant difference between the chemotactic activity of PMMA IOLs. However, chemotactic activity was significantly higher in acrylic (p<0.05) and silicone (p<0.05) IOLs compared to one of the PMMA lenses. CONCLUSIONS: This limited study has proven that chemotaxis assay is a useful tool to assess the biocompatibility of IOLs. The IOL material itself might attract inflammatory cells to its surface in the absence of surgical and host factors. As PMMA IOLs do not cause an increase in inflammatory reaction, they may be considered safe to use. Further improvement in chemical composition and surface characteristics of IOLs should reduce the inflammatory reaction and increase the biocompatibility and safety of IOLs.

Visual outcome of juvenile rheumatoid arthritis-associated uveitis in adults.

PURPOSE: Juvenile rheumatoid arthritis (JRA) is the systemic disease most frequently associated in childhood uveitis. The disease may cause several ocular complications, visual impairment, and blindness. Recent studies revealed a more favorable ocular prognosis. Our purpose was to analyze the long-term visual outcome of JRA-associated uveitis. METHODS: Ocular complications and visual outcome in adult patients with JRA-associated uveitis were evaluated. Among 18 patients included in the study, uveitis was bilateral in 12 (66.7%) and unilateral in six (33.3%), for a total of 30 eyes with ocular involvement. RESULTS: The mean durations of JRA and its associated uveitis were 24.9 and 20.5 years, respectively. All eyes (100%) had at least one ocular complication. The most frequently observed ocular complications were cataract (83.3%), band keratopathy (60%), posterior synechia (46.7%), glaucoma (33.3%), hypotony (16.7%), and macular pathology (13.3%). Final visual acuity was impaired in 40% of the eyes, poor in 20%, and totally lost in 10%. Therefore, 70% of the eyes were either visually handicapped or totally blind. Most eyes underwent at least one surgical procedure. Inflammation was active at last examination in 63.3% of eyes. All patients were still treated topically and with systemic NSAID. Sixty-one percent of the patients were using an immunosuppressive agent. CONCLUSION: JRA-associated uveitis still has a severe course and blinding potential. Patients suffer from uveitis and its complications even during the adulthood period. However, because our series represents a more severe subset of the disease, the outcome may be poorer than that of some other outcome studies.

Longterm follow-up of patients with multifocal choroiditis and panuveitis.

PURPOSE: To report the visual prognosis and longterm complications in patients with multifocal choroiditis and panuveitis (MCP). METHODS: A retrospective study was performed with patients who met inclusion criteria for MCP at the Uveitis Clinic, Royal Victoria Hospital, McGill University, Montreal, Canada. Information collected included duration of follow-up, visual acuity (VA) measured at each clinical visit, ocular and systemic treatment and ocular complications observed during follow-up. RESULTS: Nineteen patients (37 eyes) with MCP with a mean follow-up of 76.9 months were studied. Kaplan-Meier survival analysis showed a decrease in the proportion of patients with a final VA > or = 20/40 over time. Cystoid macular oedema was seen in 29.7% of the eyes and was the most frequent macular abnormality observed in our group. On the other hand, choroidal neovascularization was detected in only six (16.2%) of the eyes, but was related to VA < 20/200 in four of these eyes. Glaucoma was detected in 10.8% of the eyes. Cataract (posterior subcapsular and/or nuclear) was the most common longterm complication, occurring in 40% of affected eyes. Cataract surgery improved the VA in 83.3% of these eyes. CONCLUSION: The visual acuity of patients with MCP decreases with time. Visual loss can occur from complications following the inflammation itself and/or iatrogenic induced by the chronic use of corticosteroids.

Ultrasound biomicroscopy of pseudophakic eyes with chronic postoperative inflammation.

PURPOSE: To evaluate the ultrasound biomicroscopy (UBM) findings in pseudophakic eyes with chronic noninfectious postoperative inflammation and discuss the use of the technique in these cases. SETTING: Uveitis Service, Department of Ophthalmology, McGill University, Montréal, Québec, Canada. METHODS: Fifty-four eyes of 51 patients with chronic noninfectious postoperative inflammation were prospectively evaluated between January 1998 and September 2001. Patients with aphakia, a dislocated intraocular lens (IOL) in the posterior segment, and endophthalmitis were excluded. All patients had a UBM examination that comprised locating the IOL position, investigating the presence of lens remnants, and evaluating the anterior segment of the eye. RESULTS: Ultrasound biomicroscopic examination revealed IOL misplacement in 37 eyes (68.5%). Of these, 23 (62.2%) had a sulcus-implanted posterior chamber IOL (PC IOL), 9 (24.3%) an in-the-bag PC IOL, and 5 (13.5%) an anterior chamber IOL. Haptic misplacement was significantly higher with sulcus-implanted PC IOLs than with in-the-bag PC IOLs (P<.01). Other UBM findings included edematous ciliary body processes and hypoechogenic and/or thickened ciliary bodies in 11 eyes (20.4%), peripheral anterior synechias in 8 eyes (14.8%), a significant number of lens remnants (graded as severe) in 6 eyes (11.1%), a thick cyclitic membrane in 3 eyes (5.6%), and an early cyclitic membrane in 2 eyes (3.7%). CONCLUSIONS: Irritation of ocular tissues by an IOL was the main cause of chronic postoperative noninfectious inflammation in pseudophakic eyes. Therefore, detecting the IOL position and its relationships to ocular tissues is very important in planning the treatment. Ultrasound biomicroscopy is a practical method that accurately provides this information.