Infection and Vaccine Induced Spike Antibody Responses Against SARS-CoV-2 Variants of Concern in COVID-19-Naïve Children and Adults.

Although a more efficient adaptive humoral immune response has been proposed to underlie the usually favorable outcome of pediatric COVID-19, the breadth of viral and vaccine cross-reactivity toward the ever-mutating Spike protein among variants of concern (VOCs) has not yet been compared between children and adults. We assessed antibodies to conformational Spike in COVID-19-naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with SARS-CoV-2 Early Clade, Delta, and Omicron. Sera were analyzed against Spike including naturally occurring VOCs Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1, and variants of interest Epsilon, Kappa, Eta, D.2, and artificial mutant Spikes. There was no notable difference between breadth and longevity of antibody against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants compared with naturally infected individuals. Delta-infected patients had an enhanced cross-reactivity toward Delta and earlier VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 antibody titers were generated after Omicron infection, cross-reactive binding against Omicron subvariants was reduced across all infection, immunization, and age groups. Some mutations, such as 498R and 501Y, epistatically combined to enhance cross-reactive binding, but could not fully compensate for antibody-evasive mutations within the Omicron subvariants tested. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance in the context of limited vaccine boosters available to the pediatric population.

Feasibility and Potential for Real-Time 3D Vitreoretinal Surgery Telementoring.

PURPOSE: To demonstrate the potential for real-time, three-dimensional (3D) surgical telementoring to enhance vitreoretinal surgical education. METHODS: The 3D video feed from a high dynamic range surgical camera (NGENUITY) was run through a 4K video capture device (Magewell USB 4K) and set as the video input for a video conferencing application (Zoom). Remote surgical viewing was then performed in two-dimensions (2D) on a computer or in 3D with a virtual reality headset (Oculus Quest 2). RESULTS: Ten surgical cases were successfully live streamed in real time to two separate surgeons in the United States. Specific details of the case were visualized with low latency and interaction with the operating surgeon was possible without affecting the surgical display quality. Excluding the NGENUITY system and personal computers, ancillary equipment costs (video capture card and virtual reality headset) were kept to below $1,000. CONCLUSION: Our study demonstrates that 3D surgical video streaming can be achieved in real time with minimal latency through the use of low-cost video capture equipment and video conferencing/streaming software. The use of this technology gives educators the ability to mentor trainees without the traditional geographic and physical constraints of in-person surgical viewing.

ANALYSIS OF PARS PLANA VITRECTOMY INCISIONS USING LIVE BACTERIA.

PURPOSE: To analyze small gauge pars plana vitrectomy sclerotomies using live bacteria transformed with green fluorescent protein (GFP). METHODS: Twenty-eight human cadaver eyes were specially harvested for this study. Small gauge vitrectomy was performed on each eye and the wounds were closed with various techniques (sutured, sutureless, and cauterization). Live Staphylococcus epidermidis that has been transformed with a green fluorescent protein was applied to the overlying conjunctival surface. Analysis of all vitreous samples was analyzed with confocal laser microscopy to identify the presence of bacteria. All wounds were analyzed histopathologically. RESULTS: A high concentration of bacteria was noted in 2 of 3 eyes in the sutureless, 23-G perpendicular incision group postinoculation. There were no bacteria detected in any postvitrectomy sample that were closed with cautery or a beveled incision. No bacteria were found in postvitrectomy samples of sutureless 27-G perpendicular incisions and sutureless 27-G beveled incisions. Finally, there were no bacteria detected in both eyes with 23-G perpendicular incisions that had a partial air-fill. CONCLUSION: Live bacteria can be effectively used to analyze wound integrity. Closing sclerotomy sites with cautery proved effective in a model using fresh, human cadaver eyes. 27-G perpendicular incisions may be just as competent as 27-G beveled incisions.

Phosphate, fibroblast growth factor 23 and retinopathy in chronic kidney disease: the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Elevated circulating concentrations of phosphate and fibroblast growth factor 23 (FGF23) contribute to the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Retinopathy is a common manifestation of microvascular disease in CKD, but its associations with phosphate and FGF23 have not been studied. We tested the hypothesis that higher serum phosphate is associated with more severe retinopathy in individuals with CKD, independent of FGF23 and known risk factors for retinopathy. METHODS: We tested the associations of serum phosphate and plasma FGF23 with retinopathy in a cross-sectional analysis of 1800 participants in the Chronic Renal Insufficiency Cohort Study who underwent fundus photography. Retinopathy severity was graded according to the Early Treatment of Diabetic Retinopathy Severity score, and retinal venous and arterial diameters were measured. RESULTS: Mean estimated glomerular filtration rate (eGFR) was 46.5 ± 15.4 mL/min/1.73 m(2), mean serum phosphate was 3.7 ± 0.6 mg/dl and median plasma C-terminal FGF23 was 133 RU/mL (interquartile range 87.2, 217.8 RU/mL). In multivariable ordinal logistic regression models, higher serum phosphate was associated with greater retinopathy severity independent of hypertension, diabetes, CKD severity and FGF23 [adjusted odds ratio of being in one higher category of retinopathy severity: 1.19 per 1 standard deviation increase; 95% confidence interval (CI) 1.05, 1.36; P = 0.007]. Presence of diabetes or hypertension did not modify the results. Higher serum phosphate was also independently associated with greater retinal venous diameter (multivariable-adjusted 1.70 µm increase per 1 standard deviation increase in phosphate; 95% CI 0.46, 2.93; P = 0.007). FGF23 levels were not independently associated with retinopathy severity or retinal venous diameter, and neither FGF23 nor phosphate was associated with retinal arterial diameter. CONCLUSIONS: Among individuals with moderate-to-severe CKD, higher serum phosphate but not FGF23 was independently associated with more severe retinopathy and microvascular retinal venous dilatation.

INFLUENCE OF VITREOMACULAR INTERFACE ON ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY USING TREAT AND EXTEND TREATMENT PROTOCOL FOR AGE-RELATED MACULAR DEGENERATION (VINTREX).

PURPOSE: To determine the influence of vitreomacular adhesion (VMA) on treatment outcomes in patients with neovascular age-related macular degeneration who were treated with anti-vascular endothelial growth factor agents using a treat and extend treatment regimen. METHODS: A retrospective consecutive case series of 204 eyes from 181 patients with a minimum of 1 year of follow-up at Wills Eye Hospital Retina Service. Vitreomacular interface characteristics were determined by spectral domain optical coherence tomography. One hundred and fifty-three eyes (75%) had no signs of VMA (non-VMA), and 51 (25%) had VMA. RESULTS: Baseline mean visual acuity was 20/133 with a mean central retinal thickness of 350.5 µm in the non-VMA group and was 20/145 with 371.8 µm in the VMA group. Mean visual acuity in the non-VMA group was 20/83 and 20/64 at Years 1 and 2, respectively (P < 0.01 to baseline). Mean visual acuity in the VMA group was 20/81 and 20/85 at Years 1 and 2, respectively (P < 0.01 to baseline). The central retinal thickness was 289.71 µm and 267 µm at Years 1 and 2, respectively (P < 0.01 to baseline) in the non-VMA group and was 305.3 µm and 289.24 µm (P < 0.01 to baseline) in the VMA group. The mean total number of injections at Year 1 for non-VMA was 7.4 compared with 8.4 in VMA (P = 0.001) and 5.5 versus 6.7 for the 2 groups in Year 2 (P = 0.027). The mean longest extension at Year 1 was 11.8 weeks compared with 10.1 week (P = 0.005) and for Year 2 was 14.1 weeks compared with 12 weeks (P = 0.041). CONCLUSION: The vitreomacular interface seems to have a significant influence on anti-vascular endothelial growth factor treatment intervals but not visual acuity or exudative control outcomes. Eyes with VMA on spectral domain optical coherence tomography at baseline may require more intensive treatment with decreased ability to extend treatment intervals.

Lasers for the treatment of intraocular tumors.

Lasers are used extensively in ophthalmology for a variety of conditions, including many choroidal and retinal tumors. With technologic advances, current therapy attempts not only to maximize survival with globe-salvaging treatment, but also to preserve vision. Each neoplasm has different indications for primary and adjuvant therapy, as well as differing laser treatment protocols. Additionally, there are numerous laser applications available for use, including laser photocoagulation, transpupillary thermotherapy (TTT), and photodynamic therapy (PDT). The current review outlines the basic principles of laser treatment for intraocular tumors, focusing on the indications, treatment protocols, efficacy, and safety, while also presenting the latest advances in intraocular tumor treatment.

Laser treatment for retinopathy of prematurity.

Retinal development involves a complex coordination of events that may be affected by premature delivery, leading to retinopathy of prematurity (ROP), a potential blinding childhood disease. The avascular retina drives further disease progression, with laser ablation reducing unfavorable anatomic outcomes as well as maintaining visual acuity. Trials have stressed the importance of early identification and treatment of threshold and high-risk prethreshold disease to improve outcomes. Retinal ablation with laser photocoagulation should involve entire treatment of avascular retina with a confluent laser spot density, avoiding skip lesions. The current review highlights the use of laser photocoagulation in the treatment of ROP.

Validation of a Flow Cytometry Live Cell-Based Assay to Detect Myelin Oligodendrocyte Glycoprotein Antibodies for Clinical Diagnostics.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG Ab) are essential in the diagnosis of MOG Ab-associated disease (MOGAD). Live cell-based assays (CBAs) are the gold standard for MOG Ab detection with improved sensitivity and specificity over fixed CBAs. A number of testing centers have used flow cytometry for its high throughput and quantitative utility. Presently, there is increasing demand to translate these research-based methods into an accredited routine diagnostic setting. METHODS: A flow cytometry live CBA was used to detect MOG Ab in patients with demyelination. Serostatuses were compared between a research-based assay and a streamlined diagnostic assay. Inter-laboratory validation of the streamlined assay was performed in an accredited diagnostic laboratory. Further streamlining was performed by introducing a borderline serostatus range and reducing the number of controls used to determine the positivity threshold. RESULTS: High serostatus agreement (98%-100%) was observed between streamlined and research-based assays. Intra- and inter-assay imprecision was improved in the streamlined assay (mean intra- and inter-assay CV = 7.3% and 27.8%, respectively) compared to the research-based assay (mean intra- and inter-assay CV = 11.8% and 33.6%, respectively). Borderline positive and clear positive serostatuses were associated with confirmed phenotypes typical of MOGAD. Compared to using 24 controls, robust serostatus classification was observed when using 13 controls without compromising analytical performance (93%-98.5% agreement). CONCLUSIONS: Flow cytometry live CBAs show robust utility in determining MOG Ab serostatus. Streamlining and standardizing use of this assay for diagnostics would improve the accuracy and reliability of routine testing to aid diagnosis and treatment of patients with demyelination.

Rarebit perimetry for bedside testing: comparison with standard automated perimetry.

BACKGROUND: Rarebit perimetry (RBP), a technique developed for the detection of early damage to the afferent visual system, has not been extensively tested at the bedside. This study was designed to test the feasibility of bedside testing with RBP in comparison with standard automated perimetry (SAP) performed in the clinic. METHODS: We tested 29 eyes of 15 subjects admitted with neurologic or neurosurgical diseases affecting the afferent visual system. RBP was performed on a laptop computer at the bedside. SAP (Humphrey field analyzer) testing was performed later in the clinic. Results were evaluated by a masked neuro-ophthalmologist. RESULTS: Visual fields corresponded between RBP and SAP in 21(72%) of the 29 tested eyes. RBP detected defects in 5 subjects who had normal visual field results on SAP. All subjects preferred RBP for convenience. CONCLUSION: RBP is a convenient method of bedside visual field testing and is no less sensitive to visual field defects in this role than SAP.

Pro-inflammatory dopamine-2 receptor-specific T cells in paediatric movement and psychiatric disorders.

OBJECTIVES: A dysregulated inflammatory response against the dopamine-2 receptor (D2R) has been implicated in movement and psychiatric disorders. D2R antibodies were previously reported in a subset of these patients; however, the role of T cells in these disorders remains unknown. Our objective was to identify and characterise pro-inflammatory D2R-specific T cells in movement and psychiatric disorders. METHODS: Blood from paediatric patients with movement and psychiatric disorders of suspected autoimmune and neurodevelopmental aetiology (n = 24) and controls (n = 16) was cultured in vitro with a human D2R peptide library, and D2R-specific T cells were identified by flow cytometric quantification of CD4+CD25+CD134+ T cells. Cytokine secretion was analysed using a cytometric bead array and ELISA. HLA genotypes were examined in D2R-specific T-cell-positive patients. D2R antibody seropositivity was determined using a flow cytometry live cell-based assay. RESULTS: Three immunodominant regions of D2R, amino acid (aa)121-131, aa171-181 and aa396-416, specifically activated CD4+ T cells in 8/24 patients. Peptides corresponding to these regions were predicted to bind with high affinity to the HLA of the eight positive patients and had also elicited the secretion of pro-inflammatory cytokines IL-2, IFN- γ, TNF, IL-6, IL-17A and IL-17F. All eight patients were seronegative for D2R antibodies. CONCLUSION: Autoreactive D2R-specific T cells and a pro-inflammatory Th1 and Th17 cytokine profile characterise a subset of paediatric patients with movement and psychiatric disorders, further underpinning the theory of immune dysregulation in these disorders. These findings offer new perspectives into the neuroinflammatory mechanisms of movement and psychiatric disorders and can influence patient diagnosis and treatment.

The Scope Of Three-Dimensional Digital Visualization Systems In Vitreoretinal Surgery.

INTRODUCTION: Significant advances in three-dimensional (3D) imaging technology have allowed for the incorporation of 3D digital displays into medical and surgical devices. Despite initial adoption of the NGENUITY® 3D Visualization System in vitreoretinal surgery, there are limited publications regarding its use. The generally accepted main benefits include improved ergonomics, enhanced surgical team communication and education, reduced retinal phototoxicity, increased depth of field, and display image manipulation. Despite these potential benefits, many retina specialists have questioned its universal applicability to a wide variety of vitreoretinal surgeries. OBJECTIVE: To report on the variety of indications and surgical efficacy of the NGENUITY® 3D Visualization System in vitreoretinal surgery via a review of surgical experience at two vitreoretinal practices in both the academic and community settings. METHODS: A retrospective review was conducted of consecutive surgical cases performed on the NGENUITY® 3D Visualization System at Massachusetts Eye and Ear Infirmary and Florida Retina Institute from June 1st, 2017 to November 1st, 2018. Age, presenting diagnosis, surgical procedure, and intraoperative details were recorded. RESULTS: 272 vitreoretinal surgeries on the Alcon NGENUITY® 3D Visualization System were identified between June 1st, 2017 and November 1st, 2018 at the participating institutions. A detailed breakdown of the indications for surgery and related procedures is reported. During all 272 cases on the 3D digital system, there were no complications attributed to the visualization system. CONCLUSION: This series illustrates the diversity of vitreoretinal surgeries that can be performed on this system without compromising surgical viewing or increasing surgical complications. The Alcon NGENUITY® 3D Visualization System possesses favorable ergonomics, illumination levels, depth of field, display filters, and trainee experience.

Effect of aflibercept on refractory macular edema associated with central retinal vein occlusion.

OBJECTIVE: To report short-term visual and anatomic outcomes of patients who were switched to aflibercept for persistent macular edema associated with central retinal vein occlusion (CRVO). METHODS: Retrospective, consecutive, interventional case series of 17 patients with persistent macular edema secondary to CRVO (defined as intraretinal edema and either <50 µm reduction in central foveal thickness [CFT] or worsening or no improvement in visual acuity [VA] compared to baseline) despite anti-VEGF treatment who were switched to aflibercept treatment. Main outcome measures included VA, anti-VEGF treatment history, and spectral-domain optical coherence tomography evaluation of macular edema and CFT. RESULTS: The mean age was 77 years, and the mean VA at CRVO diagnosis was 20/135 with a CFT of 523.4 µm. Mean number of injections before switching to aflibercept was 12.9 (range: 3-40) and mean number of months of anti-VEGF treatment before switching to aflibercept was 18.7. Mean VA at switch to aflibercept was 20/182 (p = 0.50) with mean CFT of 547.9 µm (p = 0.66). Mean aflibercept injections were 4.0, and mean follow-up from switch to last follow-up was 5.2 months. Final mean VA was 20/115 (p = 0.017), with a CFT of 315.2 µm (p = 0.0012). Of the patients, 35.2% gained ≥3 lines. 29% of patients had complete resolution of macular edema, and the mean change in CFT was -233 µm. CONCLUSIONS: Aflibercept appears to have a beneficial effect on anatomic and VA outcomes in a subset of patients with macular edema secondary to CRVO that is refractory to treatment with bevacizumab and/or ranibizumab.

Bilateral Straatsma syndrome with nystagmus.

PURPOSE: This case report presents a rare case of bilateral Straatsma syndrome with nystagmus and documents additional findings related to spectral domain optical coherence tomography and ocular fundus images. METHODS: Case report with fundus photography, fluorescein angiography, indocyanine green angiography, and spectral domain optical coherence tomography correlations. RESULTS: A 22-year-old man presented with extensive bilateral myelination of the retinal nerve fiber layer that encompassed both posterior poles. The patient had concomitant ocular findings of high myopia, strabismus, amblyopia, and congenital nystagmus. CONCLUSION: This case describes an unusual presentation of Straatsma syndrome and investigates the clinical features of this disease. The patient's constellation of findings is most easily explained as bilateral myelination serving as the catalyst for the associated findings of myopia and nystagmus.

Efficacy of intravitreal ocriplasmin on vitreomacular traction and full-thickness macular holes.

PURPOSE: To analyze a single center's experiences with ocriplasmin on vitreomacular traction (VMT) and the rate of VMT release, full-thickness macular hole (full-thickness MH) closure, and best-corrected visual acuity (BCVA) changes. DESIGN: Retrospective interventional case series. METHODS: Single-center study of 58 eyes of 56 patients who received intravitreal ocriplasmin for VMT with or without full-thickness MH. VMT release, full-thickness MH closure, visual acuity changes, and anatomic characteristics on spectral-domain optical coherence tomography (SD OCT) were analyzed. RESULTS: VMT resolved in 29 of 58 eyes (50%) and nonsurgical closure of full-thickness MH was achieved in 4 of 15 eyes (27%). Mean logMAR BCVA among all treated eyes improved from 0.51 (20/65) at baseline to 0.36 (20/46) at final follow-up (P = .0018) with mean follow-up of 8.7 months. When compared to eyes without VMT release, eyes with successful vitreomacular release had a better pretreatment BCVA (20/48 vs 20/89, P = .004) and final follow-up BCVA (20/31 vs 20/68, P = .0001). Improvement in BCVA was significant in eyes with VMT release (P = .0001). Transient ellipsoid zone changes were noted in 26% of treated eyes (n = 15), of which 14 had successful VMT release. Transient subfoveal fluid accumulation was noted in all these patients with vitreomacular release. Mean time to resolution of ellipsoid zone changes was within 38 days. CONCLUSION: In clinical practice, intravitreal injection of ocriplasmin achieved VMT release in approximately one half of treated eyes, with a 27% closure rate for full-thickness MH. Transient ellipsoid changes were evident in 26% of treated eyes, more common in eyes with successful VMT release.

Spectrum of Retinal Vascular Diseases Associated With Paracentral Acute Middle Maculopathy.

PURPOSE: To evaluate the spectrum of retinal diseases that can demonstrate paracentral acute middle maculopathy and isolated ischemia of the intermediate and deep capillary plexus. DESIGN: Retrospective, multicenter, observational case series. METHODS: This is a retrospective case series review of 9 patients (10 eyes) from 5 centers with paracentral acute middle maculopathy lesions and previously unreported retinal vascular etiologies. Case presentations and multimodal imaging, including color photographs, near-infrared reflectance, fluorescein angiography, spectral-domain optical coherence tomography (SD OCT), and orbital color Doppler imaging, are described. Baseline and follow-up findings are correlated with clinical presentation, demographics, and systemic associations. RESULTS: Five men and 4 women, aged 27-66 years, were included. Isolated band-like hyperreflective lesions in the middle retinal layers, otherwise known as paracentral acute middle maculopathy, were observed in all patients at baseline presentation. Follow-up SD OCT analysis of these paracentral acute middle maculopathy lesions demonstrated subsequent thinning of the inner nuclear layer. Novel retinal vascular associations leading to retinal vasculopathy and paracentral acute middle maculopathy include eye compression injury causing global ocular ischemia, sickle cell crisis, Purtscher's retinopathy, inflammatory occlusive retinal vasculitis, post-H1N1 vaccine, hypertensive retinopathy, migraine disorder, and post-upper respiratory infection. CONCLUSION: Paracentral acute middle maculopathy lesions may develop in a wide spectrum of retinal vascular diseases. They are best identified with SD OCT analysis and may represent ischemia of the intermediate and deep capillary plexus. These lesions typically result in permanent thinning of the inner nuclear layer and are critical to identify in order to determine the cause of unexplained vision loss.

Models and discovery strategies for new therapies of retinoblastoma.

INTRODUCTION: Retinoblastoma is the most common primary intraocular malignancy in children. Treatment success approaches 100% at specialized centers with globe-salvaging modalities. Primary management of retinoblastoma consists of chemoreduction with local consolidation, although newer techniques include local delivery via intra-arterial chemotherapy, periocular, or intravitreal injection. Animal models have played an integral role in the understanding of retinoblastoma tumorigenesis and have contributed to the development of globe-salvaging treatments. AREAS COVERED: This review focuses on the use of models and discovery strategies on translational research in retinoblastoma. The article reviews gene expression profiling, knockout models, and transgenic animal models. In addition, the review discusses translational applications of hyperthermia, chemotherapy (systemic and local delivery), radiation therapy, and novel targets such as hypoxia, angiogenesis, cellular metabolism, and tumor suppressor functions. EXPERT OPINION: Retinoblastoma treatment success has been driven by translational research using novel animal models and discovery strategies. Future developments require further understanding of the unique genetic events that result in tumor growth and development, as well as an understanding of the complex interactions of tumor cells with the local tumor microenvironment and how this affects tumor growth, metastasis, and response to treatment.

Combination therapy with triamcinolone acetonide and bevacizumab for the treatment of severe radiation maculopathy in patients with posterior uveal melanoma.

PURPOSE: To evaluate the role of intravitreal triamcinolone acetonide in patients who developed severe, visually compromising radiation maculopathy or progressed despite anti-angiogenic treatments. METHODS: An Institutional Review Board approved, consecutive, retrospective study from 2006 to 2009 of patients who developed severe, visually compromising radiation retinopathy manifesting as macular edema secondary to iodine-125 plaque brachytherapy for posterior uveal melanoma, were treated with a combination of intravitreal bevacizumab and intravitreal triamcinolone. Patients were evaluated with spectral domain optical coherence tomography (SD-OCT) at 2-4 month intervals following plaque removal. Treatment with intravitreal bevacizumab commenced at the first signs of visually compromising macular edema diagnosed with SD-OCT. Triamcinolone acetonide was administered to patients with severe maculopathy as consolidative therapy, or for patients that were refractory to repeated bevacizumab injections with persistent or worsening cystoid macular edema and lack of improvement or progressive worsening of best corrected visual acuity (BCVA). RESULTS: Twenty-five patients were evaluated after receiving a combination of intravitreal bevacizumab and triamcinolone. Initial treatment commenced at a mean of 14.5 (range of 2-42) months after plaque brachytherapy. Patients were given a mean of two injections (range 1-6) of triamcinolone acetonide, and a mean of 8.8 bevacizumab injections (range of 1-26) with a mean follow-up of 31.2 months. Radiation maculopathy upon first detection had a mean SD-OCT grade of 3.6 (median = 4), with an associated mean entry level BCVA of 20/70. Visual acuity at time of first intravitreal triamcinolone was 20/138. At last follow-up (mean of 45.5 months after plaque brachytherapy) mean BCVA was 20/136; however, 9 of 25 (36%) patients who presented with severe radiation maculopathy demonstrated 20/50 or better vision at last follow-up. CONCLUSION: This case series suggests a beneficial role for intravitreal triamcinolone as a consolidation treatment for patients who present with severe radiation maculopathy or as an adjuvant to bevacizumab for refractory or progressive maculopathy.

Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detachment.

BACKGROUND: The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma. METHODS: This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity. RESULTS: One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40). Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40) at 4 months, with stabilization to 20/57 (median 20/40) at 8 months, 20/56 (median 20/30) at 12 months, and 20/68 (median 20/50) at 24 months. Tumor volume following combined therapy was shown to be reduced by 22.2% at 3 months, 28.9% at 6 months, 39.3% at 12 months, and 52.2% at 24 months (all P < 0.001). All patients tolerated the procedure well without systemic side effects. CONCLUSION: Intravitreal bevacizumab may be used as an adjuvant agent following plaque brachytherapy. Treated choroidal melanomas show reduction in tumor volume as well as resolution of exudative retinal detachments.

Microincisional vitrectomy for retinal detachment in I-125 brachytherapy-treated patients with posterior uveal malignant melanoma.

PURPOSE: To analyze functional and anatomical outcomes following 23/25(+) gauge microincisional pars plana vitrectomy surgery (MIVS) in patients with radiation-related retinal detachment after successful 125-iodine (I-125) brachytherapy treatment for malignant uveal melanoma. PATIENTS AND METHODS: Retrospective case series of 102 consecutive eyes of 102 patients with history of uveal melanoma treated with I-125 brachytherapy that underwent MIVS at the Bascom Palmer Eye Institute. All cases were evaluated for surgical complications and local tumor control. Extended follow-up included Snellen's best-corrected visual acuity, intraocular pressure evaluation, quantitative echography, indirect ophthalmoscopy, and fundus imaging with optical coherence tomography/wide-field photography. RESULTS: All patients had radiation-related complications, including retinal detachment (102 eyes), vasculopathy (91 eyes), optic neuropathy (32 eyes), and/or vitreous hemorrhage (8 eyes). Sixty-seven patients had vitreoretinal traction. Average follow-up after MIVS was 19.5 months, and from plaque removal was 57.7 months. Interval from plaque to MIVS was 38.1 months. Initial visual acuity was 20/258, which improved to 20/101 at 1 month, 20/110 at 3 months, 20/116 at 6 months, and 20/113 at 12 months (P < 0.05). No eyes required enucleation. Melanoma-related mortality was 0.9% (1/102). There was no intra- or extraocular tumor dissemination, and no tumor recurrence. CONCLUSION: MIVS was effective in improving visual function and anatomy in patients with radiation-related retinal detachment. Tumors decreased in size and there was no evidence of recurrence or tumor dissemination. This combined procedure addresses the modifiable causes of visual loss in patients with previously treated malignant uveal melanoma and has the potential to enhance their visual function.