Clinical and imaging biomarkers of response to intravitreal dexamethasone implant in eyes with non-infectious uveitic macular oedema.

OBJECTIVE: To investigate clinical and spectral-domain optical coherence tomography (SD-OCT) biomarkers correlating with pre-injection visual acuity (VA), post-injection VA, and the likelihood of macular oedema (MO) regression following dexamethasone (DEX) implant injection in non-infectious uveitic (NIU) patients. METHODS: Patient data from Uveitis Services in Milan, Paris, and Berlin were analysed. Eligible participants were NIU patients aged >18 years with MO as the primary indication for DEX treatment. SD-OCT scans and clinical data were collected at the time of DEX injection (pre-injection visit) and after 3 months (post-injection visit). Multivariable regression models, adjusted for pre-injection VA and lens status, were employed to explore associations. MO regression was defined as the absence of intraretinal/subretinal fluid at the post-injection visit. RESULTS: Our analysis comprised data from 173 DEX treatments, encompassing 103 eyes from 80 patients, with 38 eyes (37%) receiving repeated DEX injections. The absence of the ellipsoid zone (EZ) layer and disorganisation of the inner retinal layers (DRIL) were associated with worse pre- (+0.19 LogMAR, 95% CI 0.01-0.38, p = 0.06, and +0.10 LogMAR, 95% CI 0.02-0.21, p = 0.01) and post-injection VA (+0.33 LogMAR, 95% CI 0.08-0.57, p = 0.01, and +0.17 LogMAR, 95% CI 0.01-0.32, p = 0.04). EZ disruption and DRIL increased significantly (p = 0.01 and p = 0.04), and the chance of gaining ≥5 letters declined in eyes undergoing repeated DEX (p = 0.002). The rate of MO regression after each DEX was 67%. Prolonged MO duration (OR = 0.75/each year, p = 0.02) was associated with reduced likelihood of MO regression. Subretinal fluid was associated with higher rate of MO regression (OR = 6.09, p = 0.01). CONCLUSION: Integrity of the inner and outer retina is associated with better visual response to DEX. Long-standing or recurrent MO is associated with less chance of both visual and anatomic response. Timely treatment is necessary to maximise the outcomes of MO in NIU patients.

Behavior of SD-OCT Detectable Hyperreflective Foci in Diabetic Macular Edema Patients after Therapy with Anti-VEGF Agents and Dexamethasone Implants.

PURPOSE: Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. METHODS: A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group, n = 40 eyes) or dexamethasone implant (DEX group, n = 19). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. RESULTS: DME decreased in 75% of patients in the VEGF (455.5 µm vs. 380.8 µm, p = 0.02) and in 95% of patients in the DEX group (471.6 µm vs. 381.9 µm, p = 0.007). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1, p = 0.07) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9, p = 0.02) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. CONCLUSION: The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.

Corneal higher-order aberrations after cataract surgery: Manual phacoemulsification versus femtosecond-laser assisted technique.

PURPOSE: To compare and evaluate corneal higher-order aberrations (c-HOA) between conventional manual phacoemulsification (Phaco), femtosecond laser-assisted cataract surgery (FLACS), and femtosecond laser-assisted cataract surgery with astigmatic keratotomy (FSAK). METHODS: In this retrospective single center study, 53 healthy individuals with cataract (73 eyes) underwent phacoemulsification with implantation of an intraocular lens. Three groups were formed: group A, Phaco (n = 27 eyes of 21 patients); group B, FLACS (n = 25 eyes of 15 patients); group C, FSAK (n = 21 eyes of 17 patients). An iTrace aberrometer (Tracey Technologies, Houston, TX, USA) was used to perform aberrometry with a pupil scan size of 5.0 mm. We used ANOVA analysis and the paired sample t-test for statistical analysis. RESULTS: There was no difference in total c-HOA between the groups prior to surgery (F(2,66) = 2.2, p = 0.128), but some evidence for a difference between the groups after surgery (F(2,65) = 3.87, p = 0.025). After surgery, total c-HOA increased in all groups, but the greatest increase occurred FSAK. CONCLUSION: Manual phacoemulsification and femtosecond laser-assisted cataract surgery seem to have less impact on corneal higher-order aberrations than the combination of femtosecond laser-assisted cataract surgery with astigmatic keratotomy.

Findings and Graduation of Sarcoidosis-Related Uveitis: A Single-Center Study.

Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the "International Workshop on Ocular Sarcoidosis" (IWOS) criteria, ocular sarcoidosis was determined as: definite (n = 24; 28.6%), presumed (n = 33; 39.3%), probable (n = 10; 11.9%), and indefinite (n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.

Overcoming barriers of retinal care delivery during a pandemic-attitudes and drivers for the implementation of digital health: a global expert survey.

BACKGROUND/AIMS: The SARS-CoV-2 pandemic has imposed barriers to retinal care delivery worldwide. In this context, retinal services are exploring novel ways to ensure access to healthcare. METHODS: We conducted a worldwide survey among retinal specialists between March 31, 2020 and April 12, 2020. The expert survey was developed on the basis of focus group discussions involving retinal specialists and literature searches. It included 44 questions on alternative ways of care provision including digital health domains such as teleophthalmology, home monitoring or decentralised patient care. RESULTS: 214 retinal experts participated in the survey, of which 120 (56.1%) had more than 15 years of experience in ophthalmology. Most participants were clinicians (n=158, 73.9%) practising in Western Europe (n=159, 74%). In the majority of institutions, teleophthalmology, home monitoring and decentralised patient care have not been implemented before the pandemic (n=46, 21.8.1%; n=64, 29.9%; n=38, 19.1%). During the pandemic, the use of teleophthalmology and home monitoring increased significantly (n=105, p<0.001; n=90, p<0.001). In the subgroup of institutions reporting no teleophthalmology service before and implementing a service during the pandemic (34/70, 48.6%), reimbursement was the sole significant parameter (OR 9.62 (95% CI 2.42 to 38.16); p<0.001). CONCLUSION: Digital health is taking the centre stage tackling unpreceded challenges of retinal care delivery during the SARS-CoV-2 pandemic and may sustainably change the way we practice ophthalmology.

Sympathetic Ophthalmia - a Contribution to Immunology, Clinic and Current Imaging. / Sympathische Ophthalmie ­ ein Beitrag zur Immunologie, Klinik und aktuellen Bildgebung.

BACKGROUND: Sympathetic ophthalmia (SO) is a rare inflammation of an operated or injured eye that spreads to the fellow eye. It is typically a bilateral granulomatous panuveitis. The traumatized eye is referred to as inciting eye and the fellow eye as sympathizing eye. The pathophysiology of the disease is not entirely understood, but there is strong evidence of an autoimmune genesis. PATIENTS/MATERIAL AND METHODS: A selective literature search on epidemiology, immunology, clinical features and risk factors of SO was carried out. In addition, our own experience using multimodal imaging for this clinical entity was introduced. RESULTS: In the literature, the incidence after traumatic eye injuries is 0.1 - 3% and approximately 0.01% after intraocular surgery. Among the iatrogenic causes, vitreoretinal surgery has the highest rate of SO, presumably due to disruption of the blood-retinal barrier and involvement of retinal and choroidal tissue, which are susceptible to anterior traction, phthisis and chronic inflammation. In 90% of patients, the disease develops within a year following the eliciting event and is associated with a potentially bilateral risk of blindness. Typical symptoms include bilateral visual impairment with photophobia, dull pain and photopsia. The spectrum of clinical manifestations ranges from granulomatous anterior uveitis and vitritis, to choroiditis, serous retinal detachment and Dalen-Fuchs nodules in the context of posterior involvement. The diagnosis of SO is generally based on clinical presentation and is supported by imaging methods. These primarily comprise fluorescein and indocyanine green angiography, which are increasingly being supplemented by non-invasive methods such as optical coherence tomography. They can provide important information for assessment of severity, differential diagnosis as well as for disease monitoring. The differential diagnosis includes i. a. Vogt-Koyanagi-Harada syndrome, ocular sarcoidosis and the rare phacoanaphylactic endophthalmitis. Immediate systemic high-dose steroid therapy is used as initial treatment. The course of the disease is often relapsing to chronic progressive. Immunomodulators such as ciclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil, and biologics are increasingly being used and contribute to the significantly better prognosis of the disease. Generally, SO can be triggered by any kind of intraocular intervention. CONCLUSION: SO remains a threatening clinical diagnosis that poses diagnostic and therapeutic challenges. It can be triggered post-traumatic, but also any intraocular surgery. This should be taken into account when assessing the indication for intraocular eye surgery, especially in eyes with reduced visual outcome.

[Anterior Uveitis: Clinic, Diagnostic Procedure and Treatment Options]. / Anteriore Uveitis: Klinik, diagnostisches Vorgehen und Behandlungsoptionen.

Anterior uveitis involves inflammation of the iris and/or ciliary body and is the most common intraocular inflammation in ophthalmological practice. It can be attributed to an infectious or immune-mediated genesis or be associated with systemic diseases. Anamnesis and (guiding) findings during the slit lamp examination often already provide important information on pathogenesis and thus on further diagnostic clarification and therapy. This includes the assessment of laterality, acute or chronic course of the disease and morphological criteria (granulomatous/non-granulomatous). The guideline-compliant procedure recommends further diagnosis with targeted laboratory diagnostics and, if necessary, consultative examinations if the disease recurs. This is important in order to pursue a targeted treatment approach and to recognize comorbidities.

Virus-associated anterior uveitis and secondary glaucoma: Diagnostics, clinical characteristics, and surgical options.

In this retrospective, single-center, observational study, we compared the clinical characteristics, analyzed the glaucoma development, and the glaucoma surgery requirement mediators in patients with different virus-associated anterior uveitis (VAU). In total, 270 patients (= eyes) with VAU confirmed by positive Goldmann-Witmer coefficients (GWC) for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella virus (RV), and multiple virus (MV) were included. Clinical records of these patients were analyzed. Demographic constitution, clinical findings, glaucoma development, and surgeries were recorded. The concentrations of 27 immune mediators were measured in 150 samples of aqueous humor. The GWC analysis demonstrated positive results for CMV in 57 (21%), HSV in 77 (29%), VZV in 45 (17%), RV in 77 (29%), and MV in 14 (5%) patients. CMV and RV AU occurred predominantly in younger and male patients, while VZV and HSV AU appeared mainly with the elderly and females (P<0.0001). The clinical features of all viruses revealed many similarities. In total, 52 patients (19%) showed glaucomatous damage and of these, 27 patients (10%) needed a glaucoma surgery. Minimal-invasive glaucoma surgery (MIGS) showed a reliable IOP reduction in the short-term period. In 10 patients (37%), the first surgical intervention failed and a follow-up surgery was required. We conclude that different virus entities in anterior uveitis present specific risks for the development of glaucoma as well as necessary surgery. MIGS can be suggested as first-line-treatment in individual cases, however, the device needs to be carefully chosen by experienced specialists based on the individual needs of the patient. Filtrating glaucoma surgery can be recommended in VAU as an effective therapy to reduce the IOP over a longer period of time.

Immunosuppressants and/or antivascular endothelial growth factor inhibitors in punctate inner choroidopathy? Follow-up results with optical coherence tomography angiography.

PURPOSE: To report the effectiveness of treatment with antivascular endothelial growth factor (VEGF)-inhibitor and/or immunosuppressants in punctate inner choroidopathy (PIC) using standard imaging modalities and optical coherence tomography angiography (OCTA) over a time period of 16 months. METHODS: In this prospective, unmasked, single-centre study, 23 individuals with PIC underwent imaging with spectral domain OCT, fluorescein angiography, indocyanine green angiography and OCTA. Two groups were formed based on systemic treatment. In case of choroidal neovascularisation (CNV) activity, intravitreal anti-VEGF injections were carried out in both groups. RESULTS: Group I included 12 patients (24 eyes) with 18 affected eyes (75%) who did not receive any systemic therapy at baseline. Group II contained 11 patients (22 eyes) who started systemic immunosuppressive therapy on average 2 years before baseline. All eyes with recurrence of CNV or residual fluid (group I: seven eyes; group II: six eyes) received anti-VEGF agents. Group I showed a significant reduction of CNV size (p=0.0078), as well as a decrease of fluid retention (p=0.0078) on OCTA after anti-VEGF injection. Group II did not demonstrate any significant reduction of CNV size, vessel shape or fluid retention post injection. But overall, fluid accumulation was significantly lower in group II (median=0.03 mm2) than in group I (median=0.32 mm2) (p=0.0028). CONCLUSION: Immunosuppressants in addition to anti-VEGF agents showed a significant reduction of fluid accumulation, that is, reduced disease activity. We conclude that there is a benefit and effectiveness of immunosuppressants to control inflammatory secondary CNV in PIC.

Dexamethasone Inserts in Noninfectious Uveitis: A Single-Center Experience.

PURPOSE: To report the effectiveness of repeated intravitreal dexamethasone (DEX) inserts in noninfectious uveitis patients. DESIGN: Prospective, single-center, interventional clinical trial between February 2010 and March 2015. PARTICIPANTS: Patients with noninfectious uveitis with cystoid macular edema and/or vitreitis. METHODS: Patients were treated with a 700-µg intravitreal DEX insert (Ozurdex; Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months after injection. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events were recorded. MAIN OUTCOME MEASURES: Primary outcome was the reduction of CRT. Secondary outcome was the improvement in BCVA and reduction of VH. RESULTS: In total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were women (68%). The mean age of all participants was 57 years (range, 24-88 years). More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections were 1.54±0.5 (standard deviation [SD]), 1.98±0.84, and 2.46±1.1 over 12, 18, and 24 months, respectively. Central retinal thickness decreased significantly (P < 0.001) from 465 µm at baseline to 318, 342, and 388 µm after 1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a second, third, and fourth DEX insert. Patients with idiopathic uveitis and sarcoidosis benefited well from DEX inserts. The greatest overall benefit was achieved in patients with no systemic treatment and patients receiving antimetabolites and cyclosporin A. A significant VH score reduction was documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6 months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and after 3 months (P = 0.001) was seen. CONCLUSIONS: The repeated longer-term administration of DEX inserts in noninfectious uveitis patients, either alone or in combination with other therapies, led to improved CRT, BCVA, and VH. Underlying diseases and concomitant systemic therapy seem to have an impact on overall treatment benefit. Ocular complications were reversible and were managed by local treatment, with exception of cataract formation.

Intravitreal Dexamethasone for the Treatment of CMO Associated with Refractory Sclerouveitis.

PURPOSE: To assess the efficacy and tolerability of intravitreal dexamethasone 0.7 mg sustained-release insert (Ozurdex®) in patients with sclerouveitis and recurrent cystoid macula edema (CMO) refractory to treatment. METHODS: Interventional retrospective case series of five patients receiving 13 intravitreal dexamethasone inserts. RESULTS: Three of five patients presented with an associated systemic disorder, whereas two patients had idiopathic sclerouveitis. All patients received immunosuppressive therapy. The CRT mean (SD) decreased in all eyes from 428 µm (137) (baseline) to 327 µm (149) (1 month), 342 µm (155) (3 months), 297 µm (99) (6 months) and reduced scleral inflammation. No morphologic adverse changes were noted, in particular, no scleral melting or necrosis occurred. CONCLUSIONS: Intravitreal dexamethasone may be an effective and safe therapeutic option in sclerouveitis with otherwise treatment-resistant CMO. It resolves not only CMO, but also provides a reduction of scleral inflammation and ocular pain. Nonetheless, adequate immunosuppressive treatment of an underlying disease must ensue.

Real-life clinical data for dexamethasone and ranibizumab in the treatment of branch or central retinal vein occlusion over a period of six months.

PURPOSE: To evaluate the therapeutic outcome for dexamethasone implant (DEX) or intravitreal ranibizumab (IVR) injections over 6 months in patients with macular edema due to branch or central retinal vein occlusion (BRVO, CRVO), in a real-life setting. METHODS: A total of 107 patients with BRVO or CRVO were included into this retrospective single-center observational study. Patients were treated with monotherapy consisting of DEX or three monthly IVR injections following a pro re nata regimen (PRN). Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP) were compared between the two therapy groups after 1, 3 and 6 months. RESULTS: BRVO patients treated with DEX achieved a statistically significant gain in BCVA measured in logMAR after 1 month (mean gain, 95% CI: 0.21, 0.08-0.34, p = 0.001), 3 months (0.16, 0.03-0.28, p = 0.012) and 6 months (0.19, 0.07-0.32, p = 0.002), whereas patients treated with IVR showed a statistically significant BCVA gain in month 3 (mean improvement, 95% CI: 0.13, 0.01-0.26, p = 0.039) and month 6 (0.16, 0.03-0.29, p = 0.018). BCVA in CRVO patients with DEX worsened slightly at month 6 (mean worsening, 95% CI: -0.08, -0.24 to 0.08, p = 0.305), while IVR treated-patients achieved a statistically significant BCVA gain at 3 months (mean improvement, 95% CI: 0.14, 0.02-0.25, p = 0.021). Both therapies were accompanied by statistically significant CRT reductions of 150 to 200 µm (median). Adverse events reported were predictable and limited. CONCLUSIONS: In a clinical setting, comparable improvement in BCVA and CRT were observed after DEX and IVR injections for treatment of BRVO. CRVO patients showed greater benefit with IVR.

Age dependent differences in the kinetics of γδ T cells after influenza vaccination.

Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of γδ T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21 young (19-30 years) and 23 elderly (53-67 years) healthy individuals. Activated and proliferating γδ T cells, as identified by CD38 and Ki67 expression, were quantified on the days 0, 3, 7, 10, 14, 17, and 21. We observed a significantly lower number of activated and proliferating γδ T cells at baseline and following vaccination in elderly as compared to young individuals. The kinetics changes of activated γδ T cells were much stronger in the young, while corresponding changes in the elderly occurred slower. In addition, we observed an association between day 21 HAI titers of influenza A and the frequencies of Ki67+ γδ T cells at day 7 in the young. In conclusion, aging induces alterations of the γδ T cell response that might have negative implications for vaccination efficacy.