Familial Mediterranean Fever-Associated Retinal Vasculitis: A Rare Manifestation Successfully Managed with IL-1 Pathway Inhibitors.

PURPOSE: To investigate the rare manifestation of retinal vasculitis in Familial Mediterranean fever (FMF) and its correlation with specific gene mutations, particularly the MEFV gene, with a focus on the severity of phenotypes and systemic vasculitis. METHODS: A case report of a 45-year-old Armenian patient with FMF history and dual mutations (M680I and M694V) was analyzed. Clinical assessments, including ocular examinations, were conducted at various stages of the disease. Treatment modalities, including prednisone, Anakinra, and Canakinumab, were administered and their effectiveness was assessed. RESULTS: The patient presented with bilateral ocular pain and decreased vision, exhibiting acute anterior uveitis, perivascular hemorrhages resembling Roth spots, and subsequent features of persistent vascular sheathing and cotton-wool spots. Dual mutations, especially M694V, were associated with a severe phenotype and systemic vasculitis. Treatment with prednisone induced remission, and IL-1 pathway inhibition with Anakinra and Canakinumab successfully managed relapses. CONCLUSION: This case underscores the rarity of retinal vasculitis in FMF, particularly involving arteries, and highlights the correlation between specific gene mutations (M680I, M694V) and disease severity. The successful management with IL-1 pathway inhibitors suggests a potential therapeutic approach. Increased clinical awareness, further research, and reporting are crucial for optimizing the understanding and treatment of FMF-related ocular manifestations.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

Multiresistant Candida Endophthalmitis Treated with Intravitreal Caspofungin: A Case Report.

BACKGROUND: Candida endophthalmitis is a severe complication of candidemia. Currently, the recommended treatment of fungal endophthalmitis is a combination of intravitreal and systemic antifungal drugs, and in some cases vitrectomy is also required. Intravitreal therapies that are commonly used are amphotericin B and voriconazole, although recently the use of intravitreal caspofungin has been described in a few case reports. However, clinical experience with intravitreal caspofungin is still limited. CASE PRESENTATION: We report a case of bilateral candida tropicalis endophthalmitis, initially managed with repeated 100 µg/0.1 ml caspofungin intravitreal injections and posteriorly treated with pars plana vitrectomy in both eyes. CONCLUSIONS: Intravitreal caspofungin could be a safe intravitreal alternative to habitual antimycotic drugs in cases with resistant candida endophthalmitis.Abbreviations: Intensive Care Unit (ICU); Best-Corrected Visual Acuity (BCVA).

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Fundus flavimaculatus-like in myotonic dystrophy: a case report.

BACKGROUND: Myotonic dystrophy is an inherited disease characterized by progressive muscle weakness and myotonia. It is a multisystemic disorder that affects different parts of the body, including the eye. Dysfunction of ocular muscles, ptosis and cataract are the most common ophthalmologic manifestations, but it can also present with pigmentary changes in the retina. This report presents and discusses an unusual case of a pigmented pattern dystrophy simulating a fundus flavimaculatus in a patient with myotonic dystrophy. CASE PRESENTATION: We present a case of a woman with a history of myotonic dystrophy and complaints of progressive vision loss who presented bilateral retinal pigmentary changes in posterior pole and midperiphery. The characteristics and distribution of pigmented deposits, as well as ancillary tests, showed a retinal phenotype compatible with a multifocal pattern dystrophy or a fundus flavimaculatus. CONCLUSIONS: There are a few publications about retinal disorders in patients with myotonic dystrophy. When macular area is affected it tends to adopt a patterned-shape defined as butterfly dystrophy or reticular dystrophy. To our knowledge, this is the first report of a patient with myotonic dystrophy and multifocal pattern dystrophy or fundus flavimaculatus.

Differential response to intravitreal dexamethasone implant in naïve and previously treated diabetic macular edema eyes.

BACKGROUND: To identify different response patterns to intravitreal dexamethasone implants (IDI) in naïve and previously treated (PT) diabetic macular edema (DME) eyes in a real-life setting. METHODS: 342 IDI injections (203 DME eyes) were included. Number of IDI injections, percentage (%) of eyes with 1, 2, 3 and ≥ 4 injections, time to reinjections, visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were evaluated for naïve and PT DME eyes over 24 months. RESULTS: Mean number of injections was significantly lower in naïve vs PT DME eyes (1.40 ± 0.9 vs 1.82 ± 0.9, p < 0.001). The percentage of eyes receiving 1 injection was significantly higher in naïve vs PT DME eyes (76.1 vs 47.7), (p < 0.001). However, it was significantly lower for 2 (16.4 vs 29.4), or 3 injections (1.4 vs 17.6) (both p < 0.001), with no differences in eyes receiving ≥4 injections (5.9 vs 5.1 respectively, p = 0.80). Mean time to reinjection was not significantly different between both groups for the second, third and fourth injection (9.6 ± 4.0 vs 10.0 ± 5.5, p = 0.75, 13.2 ± 4.0 vs 16.0 ± 3.5, p = 0.21 and 21.7 ± 3.8 vs 19.7 ± 5.8, p = 0.55). VA scores were consistently better in naïve vs PT DME eyes at all studied timepoints, with no significant differences in CRT reduction or adverse effect rates. CONCLUSION: Naïve DME eyes received lower number of IDI injections and showed better VA levels than PT DME eyes for 24 months in a real-world setting. This data supports the IDI use in early DME stages and provide further evidence of better IDI response when used as first-line therapy.

Comparative study of penetrating keratoplasty and vitreoretinal surgery with Eckardt temporary keratoprosthesis in ocular trauma versus non-trauma patients.

PURPOSE: To evaluate the effectiveness of temporary keratoprosthesis combined with vitreoretinal surgery and penetrating keratoplasty in patients with or without trauma. METHODS: This retrospective study included 49 eyes in 49 non-trauma patients and 51 eyes in 48 ocular trauma patients who underwent penetrating keratoplasty and vitreoretinal surgery with Eckardt temporary keratoprosthesis between 2009 and 2016, with a follow-up of at least 12 months. Study variables included previous corneal, glaucoma, or retinal surgeries; various intraoperative surgical maneuvers; lens status; vitreoretinal and corneal pathology; functional outcomes; anatomical retinal reattachment; graft clarity; and need for glaucoma surgery or treatment. RESULTS: The mean age was 56 years in the non-trauma group and 42 years in the ocular trauma group. A total of 45% of the non-trauma cases and 24% of the ocular trauma cases had a single functional eye. Pseudophakic and aphakic keratopathy was diagnosed in 41% of the non-trauma group and corneal laceration in 65% of the ocular trauma group. In the ocular trauma group, injuries were open globe injury in 78%, closed globe injury in 12%, and intraocular foreign body in 10%. Retinal detachment with proliferative vitreoretinopathy was present in 39% of patients in the non-trauma group and in 35% of the ocular trauma group. Improvement or stability of visual acuity was higher among ocular trauma patients (86%) than in non-trauma patients (78%). The rate of clear corneal grafts was 49% in both groups. Retinal attachment was achieved in 90% and 78% of patients in the non-trauma and ocular trauma groups, respectively. The use of retinotomy had a positive influence on the final attached retina (p = 0.016). The placement of a scleral buckle significantly increased the risk of glaucoma (p = 0.004). Poor functional outcome was related to persistent retinal detachment (10% versus 16% in the non-trauma and ocular trauma groups, respectively), phthisis (25% versus 12%), hypotony (33% versus 18%), corneal graft end failure (51% in both groups), and secondary glaucoma (18% versus 24%). CONCLUSION: In patients with both vitreoretinal and corneal pathology, the use of Eckardt temporary keratoprosthesis combined with vitreoretinal surgery and penetrating keratoplasty resulted in improvement of visual acuity, particularly in the groups of ocular trauma and monocular patients. The high rate of retinal reattachment and the low rate of graft rejection was probably related to the use of new vitreoretinal techniques, including retinotomy in selected patients.

Long-term probability of intraocular pressure elevation with the intravitreal dexamethasone implant in the real-world.

PURPOSE: To evaluate the long-term cumulative probability of intraocular pressure (IOP) elevation with the intravitreal dexamethasone implant (IDI) when used to treat different indications: diabetic macular edema, uveitis, retinal vein occlusion. METHODS: 705 IDI injections (429 eyes) were assessed and Kaplan-Meier graphs were generated to assess: the probability of different levels of IOP elevation (IOP≥21, ≥25 or ≥35 mmHg), IOP change ≥10 mmHg, initiation of IOP-lowering treatment, glaucoma surgery, IOP change with repeat injections and IOP elevation in eyes with glaucoma and ocular hypertension (OHT). RESULTS: The cumulative probability of IOP ≥21, ≥25 and ≥35 mmHg was 50%-60%, 25%-30% and 6%-7% at 12-24 months, respectively. The probability of initiating IOP-lowering medication was 31%-54% at 12-24 months. Glaucoma and OHT eyes had a higher probability of mild IOP elevation (≥21 mmHg, 65.1%, 75% and 57.8%, p = 0.01), yet a similar moderate (≥25 mmHg, 22.3%, 28% and 30.2%, p = 0.91) and severe elevation of IOP (≥35 mmHg, 3.7%, 7.1% and 4%, p = 0.71) as normal eyes. Glaucoma surgery was required in only 0.9% cases (4/429). At baseline, 8.8% of the treated eyes had glaucoma, 6.7% OHT and 16.9% were already on IOP-lowering medication. CONCLUSIONS: In the long-term (24 months), IOP elevation is common, generally mild (30% IOP, ≥25 mmHg) and well-tolerated, resolving with topical treatment (54%) and rarely requiring surgery (0.9%).

Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review.

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept), better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy.

Clinical Manifestations and Outcomes of Syphilis-associated Uveitis in Northern Spain.

PURPOSE: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain. METHODS: Retrospective review of clinical records in eight general uveitis referral centers. RESULTS: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20-20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009). CONCLUSIONS: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good.

Management of Vision-Threatening Complications of Vasoproliferative Tumors of the Retina.

AIMS: To report the management of vision-threatening complications of vasoproliferative tumors of the retina. METHODS: Clinical records of 31 eyes of 30 patients treated at our centers from 1998 through 2013 were reviewed. The main outcome measures included: type of treatment, tumor regression, tumor relapse and final visual acuity. RESULTS: Seventeen patients (57%) underwent vitrectomy for epimacular membranes (n = 10), rhegmatogenous retinal detachment (n = 2), vitreous hemorrhage (n = 2), tractional retinal detachment (n = 1), serous retinal detachment (n = 1) and subhyaloid hemorrhage (n = 1). After the initial treatment, 10 additional surgeries were performed for vitreoretinal complications. Tumor activity was treated in all eyes either with photocoagulation or cryotherapy. Control of tumor activity was achieved in all cases, after treatment of recurrences. There were no statistically significant differences between initial and final visual acuity (p = 0.437). Recurrence showed a statistically significant association with the presence of proliferative vitreoretinopathy (p = 0.024), tumor thickness (p = 0.026), basal diameter (p = 0.031), and use of photocoagulation alone as initial treatment (p = 0.006, logistic regression). CONCLUSION: In our series, more than half of vasoproliferative tumors of the retina required surgery as the initial treatment. Recurrence was associated with tumor size, presence of proliferative vitreoretinopathy, and use of photocoagulation alone as the initial treatment.

Endoresection of a high equatorial choroidal melanoma.

PURPOSE: To describe previously unreported endoresection of a high equatorial choroidal melanoma. METHODS: Surgical case report imaged with wide-angle retinography and angiography, ecography, optical coherence tomography, and a short video of surgical procedure. RESULTS: The authors describe a 9.68-mm thick mushroom-shaped equatorial melanoma, which was successfully treated by endoresection. A wide-field lens and scleral indentation allowed complete tumor removal by the vitrectomy probe. Liquid perfluorocarbon stabilized the retina, therefore laser endophotocoagulation was applied to tumor margins and the scleral bed. Silicone oil was left as a tamponade, and a ruthenium-106 plaque for radiation therapy was sutured to the episclera. Eleven months after endoresection surgery, there were no signs of systemic or local recurrences. CONCLUSION: Endoresection of an equatorial choroidal melanoma was shown to be a safe technique in this patient, allowing the preservation of anatomy and function of the eye. It should be considered as an option for the treatment of large equatorial choroidal melanomas.

Epiretinal membrane after pars plana vitrectomy for primary pseudophakic or aphakic rhegmatogenous retinal detachment: incidence and outcomes.

PURPOSE: To compare outcomes of eyes that did or did not develop an epiretinal membrane (ERM) after repair of primary pseudophakic or aphakic rhegmatogenous retinal detachment by pars plana vitrectomy alone. METHODS: Interventional, prospective, consecutive case series. Of 312 consecutive eyes that underwent pars plana vitrectomy for primary rhegmatogenous retinal detachment, 28 (8.97%) developed ERM during the postoperative period. Best-corrected visual acuity (BCVA) and fundus examinations were performed 1 month and 3, 6, and 12 months postoperatively. RESULTS: Eyes with an ERM more often had a break at the equator (odds ratio, 3.92; 95% confidence interval, 1.3­11.2; P < 0.011). At ERM diagnosis, BCVA ranged from 20/400 to 20/25 with a mean of 20/100 (0.75 logarithm of the minimum angle of resolution), and BCVA at the final visit ranged from 20/200 to 20/25 with a mean of 20/63 (0.53 logarithm of the minimum angle of resolution). Of the 22 eyes that underwent surgical removal of the ERM, BCVA was ≥ 20/40 in 5 (22.7%) before the surgical procedure and in 13 (59%) at the final follow-up visit. CONCLUSION: The incidence of ERM after pars plana vitrectomy alone for the repair of primary pseudophakic or aphakic rhegmatogenous retinal detachment was similar to reported incidences after scleral buckling. Best-corrected visual acuity improved after surgical removal of ERM, although eyes with the macula detached had lower final BCVA.