Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

PURPOSE: To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. METHODS: This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08 months (ranged from 60 to 93 months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5 mg/0.05 ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3 months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. RESULTS: At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001). CONCLUSION: Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

Efficacy and Safety of Anti-Vascular Endothelial Growth Factor Drugs for Coats' Disease Treatment: A Systematic Review.

Purpose: The efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) treatment for Coats' disease remains controversial. This study was designed to evaluate the efficacy and safety of anti-VEGF treatment for Coats' disease. Methods: PubMed, Embase, The Cochrane Library, Clinical Trials, CNKI, and WanFang databases were systematically searched for clinical efficacy and safety studies on anti-VEGF treatment for Coats' disease through June 2021. Study selection, data extraction, and quality assessment were independently performed by 2 reviewers. Quality assessments were performed using the Joanna Briggs Institute Critical Appraisal tools and GRADE-CERQual. Results: A total of 1,501 articles were retrieved and reviewed, of which 24 case series involving 378 patients (range: 3-67 patients each with 3-71 eyes) were included in the analysis. No randomized controlled trials, case-controlled studies, or cohort studies were available for analysis. Most patients were male (60.0%-92.9%), aged 1.35-42.3 years, with a median follow-up time ranging from 3 to 63 months. Among the 24 case series, 22 reported changes in the visual acuity (VA) after anti-VEGF treatment and 21 reported safety outcomes. The results showed that VA improved in 73 patients (37.63%), was stable in 89 (45.87%), and worsening VA was observed in 12 cases (6.19%). The most common adverse event was fibrotic changes (n = 35). Systemic complications were not observed. Conclusions: The results of this study indicate that anti-VEGF drugs provide an effective and relatively safe treatment strategy for Coats' disease. However, conducting well-designed, prospective, randomized clinical trials are necessary to confirm our findings.

Adult-onset Coats disease.

Coats disease is an idiopathic retinal vasculopathy characterized by telangiectasia and aneurysm of retinal vessels along with intra and subretinal exudation and fluid. While Coats disease is classically described in young male population, there is an adult variant of Coats disease presenting in adulthood. Adult onset Coats disease have a similar presentation but a slower progression, localised lipid deposition, both peripheral and juxta-macular involvement. In this review article, we have attempted to describe in detail the characteristic clinical features, pathogenesis, investigation modalities and treatment in adult-onset Coats disease.

Tamoxifen induced maculopathy presenting like macular telangiectasia type 2 in a patient with breast cancer.

INTRODUCTION: Drug-induced crystalline maculopathy has been reported secondary to tamoxifen use for breast cancer treatment. It could be misdiagnosed as macular telangiectasia type 2 (MacTel type 2). CASE REPORT: A 56-year-old woman with a history of diabetes mellitus and breast cancer was referred to our clinic with painless, bilateral, gradual onset of central vision loss for several months. The fundus examination showed the macular pigmentary change in both eyes and a few refractile crystalline deposits in the parafoveal area in the left eye. However, the rest of the retina was normal in both eyes. MANAGEMENT AND OUTCOME: With the diagnosis of tamoxifen-induced maculopathy, the drug was discontinued and supplementary treatment was started. DISCUSSION: In this report, patient medical and drug history was an important and powerful measure. Due to the side effects of long-term use of tamoxifen, we need further studies on the need for retinal screening in these patients.

A Novel Approach to Subretinal Fluid Drainage in Coats'-Related Exudative Retinal Detachment.

Laser is effective at treating exudative retinal detachment (ERD) in Coats' disease. However, with severe ERD, the retina may be in contact with the lens. In such cases, laser can result in cataract formation. This case report of two patients treated at an academic medical center for Coats'-related ERD describes a technique of minimally invasive subretinal fluid drainage to create space between the lens and retina to avoid cataract. Transconjunctival unguarded needle drainage allowed for complete treatment of telangiectatic vessels and resulted in favorable anatomical outcomes in the patients. Transconjunctival unguarded needle drainage is a useful technique for treating severe, Coats'-related ERD, when a bullously detached retina is in contact with the lens. [Ophthalmic Surg Lasers Imaging Retina 2022; 53:407-409.].

Clinical Study of Intravitreal Injection of Anti-VEGF Drugs Combined with Triamcinolone Acetonide in the Treatment of Coats Disease.

Objective: To investigate the clinical study of intravitreal injection of anti-VEGF drugs combined with intravitreal injection of tretinoin for the treatment of Coats disease. Methods: The medical records of 90 patients (120 eyes) with Coats disease admitted to our hospital from April 2010 to June 2021 were selected as retrospective study subjects and divided into control and treatment groups according to the numerical table method. There were 45 cases and 60 eyes in each group. Among them, intravitreal tretinoin drug was injected into the control group, and anti-VEGF drug was injected into the vitreous sclera of the treatment group on the basis of the control group. Results: Before treatment, the differences in visual acuity changes between the two groups were not statistically significant (P > 0.05). After treatment, the light perception, manipulation, and indexes of both groups were significantly improved, and the treatment group was significantly better than the control group. This difference was statistically significant (P < 0.05) for statistical study comparison. The effective rate of 95.56% in the treatment group was significantly higher than that of 86.67% in the control group, and the complication rate was significantly lower than that of the control group, with statistically significant differences (P < 0.05). Conclusion: Intravitreal injection of anti-VEGF drugs combined with tretinoin injection can significantly improve the clinical efficacy of patients with Coats disease and improve visual acuity and central retinal thickness, which has certain reference value for the clinical treatment of Coats disease.

One-year follow-up of optical coherence tomography angiography microvascular findings: macular telangiectasia type 2 versus tamoxifen retinopathy.

PURPOSE: To compare microstructural and microvascular changes in eyes with macular telangiectasia type 2 (MacTel2) and in those with tamoxifen retinopathy (TR) at baseline and at the 1-year follow-up using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: We followed up patients diagnosed with MacTel2 or TR for at least 1 year. We included 17 patients with MacTel2 (31 eyes) and 15 with TR (25 eyes) who discontinued tamoxifen use after a TR diagnosis. We performed OCT and OCTA at baseline and after 1 year. RESULTS: Patients with MacTel2 and TR showed intraretinal cavitation, ellipsoid zone (EZ) loss, and capillary telangiectasia in the superficial and deep plexuses. EZ disruption predominantly affected the temporal region in MacTel2 (32%) and was limited to the foveal center in TR (24%). Vascular density (VD) was significantly reduced within the deep temporal parafovea and superficial fovea in MacTel2 and TR eyes, respectively. After 1 year, the MacTel2 eyes showed enlarged EZ loss, proliferative vascular invasion, and increased VD (p = 0.021) in the temporal deep plexus compared with TR eyes. CONCLUSIONS: After 1-year follow-up, the MacTel2 eyes showed proliferative vascular remodeling, particularly in the temporal parafovea of the deep plexus with EZ loss progression, whereas the TR eyes maintained their baseline capillary rarefaction.

Plentiful melanin pigment containing histiocyte-like cells in Coats disease: Awareness avoids diagnostic pitfall.

Coats disease is an exudative retinal vasculopathy characterised by presence of yellow-golden deposits in the retina and retinal detachment. Subretinal fluid drainage performed as a part of therapeutic management makes the fluid amenable to cytological examination. Infection by Toxoplasma may closely simulate the ocular symptoms seen in Coats disease. Awareness of the cytological findings in Coats disease helps to clinch accurate diagnosis. We herein present a case of Coats disease with many histiocyte-like cells with plentiful intracytoplasmic melanin pigment in cytology smears from subretinal fluid, where cytological diagnosis was challenging and a correct diagnosis was made with the aid of ancillary techniques.

TWO-YEAR RESULTS OF INTRAVITREAL INJECTIONS OF AFLIBERCEPT IN COATS DISEASE: A CASE REPORT.

PURPOSE: To report long-term results of treatment with intravitreal injections of aflibercept in a newly diagnosed case of Coats disease. METHODS: An 18-year-old man presented to the retina clinic of our hospital complaining of blurred vision in the right eye for the past 3 months. His past medical and ocular history were unremarkable. The best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye. Fundoscopy in the right eye revealed extensive macular edema with a circinate ring of hard exudates in the posterior pole temporally to the macula. Optical coherence tomography demonstrated macular edema with subretinal fluid. Peripheral telangiectasias and light bulb aneurysms in the inferior temporal arcade as well as in the nasal far periphery were found in the right eye in fluorescein angiography, confirming the diagnosis of stage 2B Coats disease. The left eye was normal. RESULTS: The original therapeutic strategy proposed was antivascular endothelial growth factor injections in the right eye, followed by laser photocoagulation. However, the patient did not consent to laser treatment and was treated with aflibercept monotherapy with 8 monthly intravitreal injections of aflibercept, followed by 6 injections every 2 months for a total of 14 injections over a period of 2 years. The best-corrected visual acuity in the right eye improved to 20/25 while optical coherence tomography imaging revealed significant decrease in retinal thickness with resolution of macular edema, and fluorescein angiography demonstrated prominent regression of aneurysms and leakage. CONCLUSION: To the best of our knowledge, this is the first case treated with aflibercept monotherapy, suggesting the significant role of vascular endothelial growth factor in vascular permeability in Coats and supporting the rationale that antivascular endothelial growth factors are a valuable therapeutic option for Coats disease.

Resolution of Foveal Lipid Deposition in Adult-Onset Coats Disease With Combined Focal Laser Photocoagulation and Anti-VEGF Therapy.

A major cause of poor visual prognosis in Coats disease is the formation of fibrovascular changes following dense foveal lipid deposition. The authors document the multimodal imaging findings of a 38-year-old woman and a 23-year-old man with adult-onset Coats disease who presented with macular edema and foveal lipid accumulation. Thermal laser targeting individual capillary macroaneurysms combined with intravitreal anti-vascular endothelial growth factor (VEGF) therapy was performed. Although there was a subsequent increase in foveal lipid immediately following the resolution of macular edema, these lipids largely resolved, leaving behind no evidence macular neovascular fibrosis. This report highlights the potential protective effect of combination therapy with thermal laser and intravitreal anti-VEGF therapy for macular exudation associated with Coats disease. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:396-399.].

Coats disease with retinal neovascularization under subfoveal nodule: optical coherence tomography-angiography findings before and after ranibizumab treatment.

We conducted retinal neovascularization under subfoveal fibrotic nodule for Coats disease by using optic coherence tomography-angiography before and after ranibizumab treatment. Our patient was an 8-year-old boy who was referred with suspicious left retinal mass. His visual acuity was 20/400 in the left eye and 20/20 in the right eye at the time of admission. Posterior segment evaluation of the left eye revealed telengiectatic vessels at the inferotemporal region of the peripheral retina with hard exudates around the optic disc and macula typical for Coats disease. His optic coherence tomography revealed a subfoveal fibrotic nodule after ranibizumab injections and laser photocoagulation treatment. The optic coherence tomography-angiography results revealed neovascularization under the subfoveal nodule at the superficial vascular complex layer. After 3 intravitreal ranibizumab injections, his neovascularization regressed on optic coherence tomography-angiography and his visual acuity improved. To the best of our knowledge, this is the first report demonstrating neovascularization under the subfoveal fibrotic nodule in Coats disease on the basis of comparative with the help of optic coherence tomography-angiography before and after the treatment.

INTRAVITREAL RANIBIZUMAB INJECTION AND RETINAL LASER PHOTOCOAGULATION TREATMENT FOR ADULT-ONSET COATS DISEASE.

PURPOSE: To describe the evolution of a case of adult-onset Coats disease and the results of treatment with intravitreal ranibizumab and laser photocoagulation. METHODS: Observational case report. CASE REPORT: A 17-year-old girl presented with vision loss in her right eye (20/50) showing aneurysmatic and abnormal telangiectatic vessels associated with profuse lipid exudation and serous retinal detachment within the temporal posterior pole. The diagnosis of Coats disease was established and therapy with intravitreal injections of ranibizumab and photocoagulation was initiated achieving control of the exudative manifestations leading to restoration of visual acuity (20/20). CONCLUSION: Treatment with antiangiogenic agents before laser photocoagulation may be useful for treatment of adult-onset Coats disease.

Levels of cytokines in the aqueous humor guided treatment of refractory macular edema in adult-onset coats' disease.

BACKGROUND: Two cases with refractory macular edema secondary to adult-onset Coats' disease underwent unsatisfactory treatment by intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs and retinal photocoagulation. CASE PRESENTATION: The authors highlight the guiding effect of the measurement of cytokines in the aqueous humor for the treatment of adult-onset Coats' disease with refractory macular edema. In the two cases, typical Coats' disease changes, including telangiectasis, subretinal exudation and macular edema were observed. Initial treatment consisted of intravitreal anti-VEGF drugs and retinal laser photocoagulation; however, the response was poor. Then, the aqueous humor was acquired and the cytokine concentrations were measured (Flow Cytometry Analysis, Beijing Giantmed Medical Diagnostics Lab). When the cytokine levels were tested every time there would be quality control, with a fixed concentration of cytokines samples to detect before the results reported. A low level of VEGF and a high level of inflammatory cytokines were found. Then, treatment was switched to intravitreal injection of dexamethasone implant (Ozurdex®) (Allergan, Inc., Irvine, Calif., USA), which resulted in resolution of the refractory macular edema and improvement of visual acuity in both cases. CONCLUSIONS: For refractory macular edema secondary to adult-onset Coats' disease, measurement of the levels of VEGF and inflammatory cytokines can help clinic doctors precisely investigate the molecular mechanism of macular edema and thereby find a suitable treatment.

Case report: internal limiting membrane drape sign masking by foveal detachment in macular telangiectasia type 2.

BACKGROUND: Internal limiting membrane (ILM) drape sign is an important OCT characteristic of Macular telangiectasia type 2 (MacTel 2). Described here is a case where masking of the ILM drape sign occurred with bilateral foveal detachments in a patient with MacTel 2. CASE PRESENTATION: A 64-year old female was diagnosed with MacTel 2, four years prior to the current presentation on the basis of an OCT demonstrating bilateral ILM drape sign. Fluorescein angiography showed bilateral dilated, ectatic capillaries and late phase dye leak. At the current presentation there was bilateral gradual visual impairment over two months due to bilateral foveal detachments. Treatment with intravitreal Bevacizumab resulted in unmasking of the pre-existing ILM drape sign at 12 weeks. Visual acuity was reduced to counting fingers in the left eye with the neovascular membrane as a consequence of sub-retinal fibrosis, while the right eye maintained a vision of 6/12. A difference in the stage of the disease at presentation determined the long-term visual outcome after seven years of observation. CONCLUSION: Foveal detachment can influence the OCT detectability of pre-existing foveal cystoid lesions. Visual prognosis at the final follow up was consistent with the interocular disparity of the disease stage at presentation.

Refractory adult Coats disease treated with dexamethasone intravitreal implant: A case report.

INTRODUCTION: Coats disease is a sporadic, retinal vascular abnormality, causing blindness. Several interventional methods, including laser photocoagulation, have been proposed; however, the use of intravitreal dexamethasone in refractory Coats disease is not well described. PATIENT CONCERNS: A 38-year-old man presented with a painless reduction in visual acuity in his right eye, commencing 15 days prior to initial assessment. DIAGNOSIS: Clinical manifestations and multimodal imaging indicated Coats disease. INTERVENTIONS: Retinal laser photocoagulation was performed in the nonperfused areas, 15 months later, the exudative retinal detachment, and macular edema remained, the patient was then treated with an intravitreal slow-release dexamethasone implant. OUTCOMES: The exudative retinal detachment and macular edema had resolved, and the BCVA had also improved. CONCLUSION: Dexamethasone intravitreal implantation was effective in treating refractory Coats disease.

Beyond Performance Metrics: Automatic Deep Learning Retinal OCT Analysis Reproduces Clinical Trial Outcome.

PURPOSE: To validate the efficacy of a fully automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2). DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: A total of 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to 1 of 2 treatment groups METHODS: The ellipsoid zone (EZ) defect areas were measured on spectral domain OCT images of each eye at 2 time points (baseline and month 24) by a fully automatic, deep learning-based segmentation algorithm. The change in EZ defect area from baseline to month 24 was calculated and analyzed according to the clinical trial protocol. MAIN OUTCOME MEASURE: Difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups. RESULTS: The difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups measured by the fully automatic segmentation algorithm was 0.072±0.035 mm2 (P = 0.021). This was comparable to the outcome of the clinical trial using semiautomatic measurements by expert readers, 0.065±0.033 mm2 (P = 0.025). CONCLUSIONS: The fully automatic segmentation algorithm was as accurate as semiautomatic expert segmentation to assess EZ defect areas and was able to reliably reproduce the statistically significant primary outcome measure of the clinical trial. This approach, to validate the performance of an automatic segmentation algorithm on the primary clinical trial end point, provides a robust gauge of its clinical applicability.

Non-proliferative type II macular telangiectasia variant with subfoveal detachment: role of anti-VEGF therapy.

AIMS: To describe a rare variant of non-proliferative stage of type II macular telangiectasia (MacTel2) with the presence of subfoveal detachment (SFD) and its response to intravitreal antivascular endothelial growth factor (VEGF) therapy. METHODS: A retrospective case series of patients diagnosed with a rare variant of non-proliferative MacTel2 (defined as MacTel2 with the presence of SFD on optical coherence tomography (OCT) in the absence of subretinal neovascularisation, confirmed on fluorescein angiography (FA)) over a period of 2 years. Patients were studied with biomicroscopy, OCT and FA. Patients were managed either with observation or anti-VEGF therapy. RESULTS: Twenty eyes of 13 patients, all female with a mean age of 52.2±6.1 years, were diagnosed with this variant of non-proliferative MacTel2. The best-corrected visual acuity at presentation ranged from 20/20 to 20/120. Six eyes were lost to follow-up. Eight eyes were kept under observation for a mean follow-up of 7.3±2.2 months and did not show resolution. Eight eyes underwent anti-VEGF therapy with a mean number of intravitreal injections of 2±1.07 per eye during a mean follow-up of 9.38±5.5 months. All eyes showed complete resolution of SFD, with a visual improvement of ≥1 line of Snellen's acuity in 87.5% of the eyes. CONCLUSION: This is the largest series of a variant of non-proliferative MacTel2 with SFD, which shows good anatomical and functional response to anti-VEGF therapy, in comparison to observation alone. Careful evaluation of the OCT images may be helpful in predicting the visual prognosis with anti-VEGF therapy.

Visual outcomes after treatment in pediatric patients with Coats' disease.

OBJECTIVE: To report visual outcomes for children with Coats' disease after treatment. DESIGN: Retrospective case series. PARTICIPANTS: Pediatric patients with Coats' disease treated between 2000 and 2018 at a tertiary care pediatric hospital. METHODS: Review of medical records. The primary outcome was visual acuity at final follow-up. Anatomical outcomes, retreatment, and risk factors for a poor outcome were also assessed. RESULTS: There were 30 patients with Coats' disease. All cases were unilateral, and 28 (93%) were male. At presentation, 14 (47%) had stage 2 disease (retinal exudates) and 16 (53%) had stage 3 disease (subtotal or total exudative retinal detachment). All patients underwent laser photocoagulation and (or) cryopexy as primary treatment, combined with antivascular endothelial growth factor injection in 7 patients, posterior sclerotomy in 5 patients, and pars plana vitrectomy in 1 patient. Retreatment was required in 16 (53%) patients. After a median follow-up of 3.8 years, visual acuity was 20/50 or better in 6 patients (20%), 20/60 to 20/150 in 3 (10%), 20/200 to counting fingers in 8 (23%), and hand motion or worse in 14 (47%). Greater severity of disease at presentation was significantly associated with a poor visual outcome (p = 0.0001). In terms of complications, 7 (23%) eyes developed cataracts and 2 (7%) progressed to phthisis bulbi, but no patients required enucleation. CONCLUSIONS: The visual prognosis for children with Coats' disease remains poor, particularly in patients with more severe disease at presentation. The risk of severe complications and enucleation is low after treatment.