A Masquerade Case: Choroidal Hemangioma Misdiagnosed As Central Serous Retinopathy.

Purpose: To report a case of misdiagnosed choroidal hemangioma, initially treated as central serous retinopathy (CSR) complicated by choroidal neovascularization (CNV), and to improve the proper identification of this disorder. Observations: Fundus images revealed a subtle, elevated choroidal lesion with an associated exudative detachment and choroidal vascular lesion on indocyanine green (ICG) angiography. Combined treatment with photodynamic therapy (PDT) and anti-VEGF therapy led to resolution of fluid and improvement in VA from 20/50 to 20/25. Conclusion: It is critical to understand the clinical features of choroidal hemangiomas and their physical presentation on retinal testing to diagnose and treat them in a timely and appropriate manner.

Macular Hole Surgery in Dome-Shaped Maculopathy.

PURPOSE: To present a successful case of macular hole surgery in a patient with dome-shaped maculopathy (DSM). OBSERVATIONS: Patient with DSM had successful closure of a full-thickness macular hole with surgery. There was persistent subretinal fluid after the surgery, which showed some response to a combination of a diuretic and a nonsteroidal anti-inflammatory drug (NSAID). CONCLUSIONS AND IMPORTANCE: Full-thickness macular hole in DSM may be effectively managed with modern surgical techniques.

Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options.

Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15-40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

Emerging biological therapies for the treatment of age-related macular degeneration.

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over age 50 in developed countries. Current therapy for nonexudative AMD (neAMD) is aimed at modifying risk factors and vitamin supplementation to slow progression, while intravitreal anti-vascular endothelial factor (VEGF) injections are the mainstay for treatment of choroidal neovascularization in exudative AMD (eAMD). AREAS COVERED: Over the past decade, promising therapies have emerged that aim to improve the current standard of care for both diseases. Clinical trials for neAMD are investigating targets in the complement cascade, vitamin A metabolism, metformin, and tetracycline, whereas clinical trials for eAMD are aiming to decrease treatment burden through novel port delivery systems, increasing drug half-life, and targeting new sites of the VEGF cascade. Stem cell and gene therapy are also being evaluated for treatment of neAMD and eAMD. EXPERT OPINION: With an aging population, the need for effective, long term, low burden treatment options for AMD will be in increasingly high demand. Current investigations aim to address the shortcomings of current treatment options with breakthrough treatment approaches. Therapeutics in the pipeline hold promise for improving the treatment of AMD, and are on track for widespread use within the next decade.

Long-Term Outcomes of Macular Hole Repair with Triamcinolone Acetonide Visualization.

PURPOSE: To evaluate the long-term anatomic and visual outcomes of macular hole (MH) repair utilizing triamcinolone acetonide (TA) visualization of the internal limiting membrane (ILM) treated at a tertiary care retina practice. METHODS: Retrospective chart review of eyes undergoing MH repair with ILM peel utilizing TA visualization followed by gas tamponade and facedown positioning between 2014 and 2020. Pre- and post-operative visual acuity (VA), IOP, and anatomic closure based on optical coherence tomography were documented. RESULTS: Seventy-eight eyes were followed for 2.3±0.2 years after primary repair with anatomic closure in 73 (94%) eyes at their final visit and excluding eyes with pathologic myopia, 97%, and for stage 2 and small MHs, 100%. In all eyes, VA significantly improved from 0.97±0.04 (Snellen: 20/187) to 0.66±0.06 (20/91) logMAR (p < 0.0001). There were 16 eyes with 4 years of follow-up, 10 (63%) eyes achieving a VA ≥20/30 at that follow-up visit. Stage 2 and 3 MHs had significantly greater improvements in VA than Stage 4 MHs, -0.46 ± 0.06 versus -0.11 ± 0.11 logMAR (p = 0.021). Of the 13 (17%) eyes with recurrent MHs, 6 (46%) had pathologic myopia and 8 (61.5%) had associated cystoid macular edema. Cataract progression was reported in 52 (96%) phakic eyes and 2 eyes required Ahmed valve placement for management of pre-existing glaucoma. CONCLUSION: Long-term results of MH repair with TA for ILM visualization demonstrate that it is safe and effective. Visual acuity continued to improve throughout the follow-up. Pre-existing glaucoma may progress and recurrence is associated with pathologic myopia and macular edema.

Multifocal ERG and Microperimetry Changes in Response to Ranibizumab Treatment of Neovascular AMD: Randomized Phase 2 Open-Label Study.

PURPOSE: To compare monthly versus pro re nata (PRN) ranibizumab injections in the treatment of exudative macular degeneration (AMD) while assessing the utility of microperimetry (MP) and multifocal electroretinography (mfERG) testing when monitoring response to treatment. METHODS: A randomized exploratory trial comparing the efficacy of monthly versus PRN dosing of ranibizumab (0.5 mg or 2.0 mg) for patients with exudative AMD over 12 months. High-resolution optical coherence tomography (HR-OCT) studies were used to guide PRN treatment and any cystic spaces or subretinal fluid prompted retreatment. Macular function was assessed using mean sensitivity on MP and N1-P1 response density on mfERG. Best-corrected visual acuity (BCVA) was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters and anatomic response assessed with central foveal thickness (CFT) using HR-OCT studies. RESULTS: The 12-month study was completed by 43 patients in the PRN cohort and 33 patients in the monthly cohort. Mean BCVA improved by 6.0 ± 1.3 ETDRS letters in the PRN cohort compared to 7.3 ± 2.8 ETDRS letters in the monthly cohort (p=0.68). A reduction in mean CFT of 64.5 ± 13.3 and 96.3 ± 22.0 µm occurred in the PRN and monthly cohorts, respectively (p=0.22). Macular function assessed with mfERG decreased comparably in both the PRN and monthly cohorts (p=0.33). For all patients, average mean sensitivity significantly improved by 1.7 ± 0.5 dB (p<0.05) and N1-P1 response density significantly decreased by 0.52 ± 0.21 nV/deg2 (p<0.05). CONCLUSION: Both PRN and monthly treatment of exudative AMD with ranibizumab improve visual function as assessed by BCVA and MP. Macular thickening also improved as demonstrated by HR-OCT findings. However, the decreased retinal function noted by mfERG suggests that some loss of retinal function still occurs despite effective treatment. These measures of visual function may be useful in assessing retinal health and response to treatment in future clinical trials.

Outcomes of Epiretinal Membrane Removal Utilizing Triamcinolone Acetonide Visualization and Internal Limiting Membrane Forceps.

PURPOSE: To evaluate epiretinal membrane (ERM) removal utilizing internal limiting membrane (ILM) forceps and visualization with triamcinolone acetonide (TA). METHODS: Retrospective interventional case series of eyes undergoing ERM removal with TA visualization with follow-up of up to five years. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and incidence of complications were reviewed. RESULTS: A total of 132 eyes were included with 54 and 16 eyes completing 3- and 5-year follow-up, respectively. Mean BCVA and CMT improved significantly at all postoperative evaluations compared to baseline (p<0.001). Pre-operative presence of PVD did not affect outcome measures. No intraoperative complications were reported. Immediate post-operative complications included one case of sterile endophthalmitis and one case of vitreous and perimacular hemorrhage. At one year, complications included progression of cataract in phakic eyes (65.4%), steroid-induced glaucoma (2.2%), retinal tear (0.8%), recurrent ERM (4.5%), and recurrent macular edema (11.3%). No further complications were reported at three- and five-year follow-up. CONCLUSION: Combination ILM forceps and TA visualization offers an affordable and safe option for ERM removal with comparable or better outcomes than traditional methods of ERM surgery.

Initial Ten Years of Experience with the Intravitreal Dexamethasone Implant: A Retrospective Chart Review.

PURPOSE: To evaluate the initial ten years of results from the intravitreal dexamethasone implant (DEX) in patients treated for retinal vein occlusion (RVO), diabetic macular edema (DME) or uveitis. METHODS: Retrospective chart review of patients receiving DEX since its FDA approval. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure and cataract status were collected. Baseline data were collected from the initial DEX and post-treatment data at the visit at least four weeks after the last DEX. RESULTS: In total, 315 eyes received 1216 DEX over 63.9±4.6 weeks. In the branch RVO (n=90), central RVO (n=59) and DME (n=62) cohorts, BCVA improved significantly (p<0.05). The uveitis (n=154) cohort did not have a significant change in BCVA, 0.62±0.04 to 0.61±0.04 logMAR (p=0.34). Younger patients, vitrectomized eyes, and eyes without a history of glaucoma were associated with significantly better BCVA outcomes in the uveitis cohort (p<0.05). Overall, CMT decreased significantly from 376.6±6.8 to 322.7±5.0 µm (p<0.05). Intraocular pressure increased significantly (p<0.001) and the percentage of patients requiring anti-glaucoma medications increased from 33.0% to 67.6%. Of phakic eyes, 58.8% (n=63) had cataract progression or underwent surgery with those who underwent surgery experiencing a significant improvement in BCVA (p<0.05). CONCLUSION: Repeated DEX over extended follow-up offers significant anatomic benefits to all cohorts. Visual benefits are only seen in RVO, DME and select uveitis demographics.

Case Report on Giant Pars Plana Cysts Mimicking Retinal Detachment.

PURPOSE: To report a case of peripheral elevated lesions mimicking retinal detachment which were ultimately ascertained to be giant pars plana cysts through ophthalmoscopy with scleral depression. METHODS: This was a case report documented with ophthalmoscopy and Optos imaging. RESULTS: Patient initially referred for assessment of bilateral retinal detachment was found by careful ophthalmoscopy with scleral depression to have bilateral giant pars plana cysts with no frank retinal breaks. CONCLUSION: Large pars plana cysts may mimic retinal detachment or other peripheral retinal pathology. The lesions in question were found to originate from the pars plana and overhang the retina. No frank retinal breaks or associated rhegmatogenous retinal detachments were noted in either eye. Ophthalmoscopy with a complete scleral depressed exam allowed for the differentiation.

A case of Legionnaire's endophthalmitis.

Purpose: To report a case of endophthalmitis associated with Legionella Pneumophila . Case Report: A 46-year-old, highly myopic male with a complex history of recurrent retinal detachments, macular hole, cataract surgery and an infected scleral buckle in the left eye, presented with pain, redness, hypopyon and vision loss in the left eye, 14 days following blunt head trauma. Empirical treatment for endophthalmitis with intravitreal injections of Vancomycin and Ceftazidime afforded minimal improvement. He developed recurrent hypopyon and underwent vitrectomy surgery with intravitreal antibiotic injections at the time of surgery and had improvement. Intraoperative culture was positive for Legionella Pneumophila. He had continued episodes of recurrent inflammation which were quelled by intravitreal moxifloxacin injections performed every 3-10 days. He developed a recurrent RD with proliferative vitreoretinopathy (PVR) and underwent vitrectomy with silicone oil. The retina was reattached but had no light perception vision in the affected eye. Conclusion: When endophthalmitis is contracted in a work-place setting, a culture for L. pneumophila should be considered. A combination of intravitreal moxifloxacin and oral azithromycin may be effective.

Silicone oil droplets following intravitreal bevacizumab injections.

PURPOSE: To report the transient resurgence of symptomatic silicone oil droplets following intravitreal bevacizumab injections. OBSERVATIONS: We report seven patients presenting with silicone oil droplets following intravitreal bevacizumab injections. These were the first cases noted in 10 years using the same supplier of preloaded syringes in an estimated 90,413 injections performed by 7 physicians. They occurred during a 4 month period (06-10/2016), suggesting they may have been related to a batch or batches of syringes. Symptomatic floaters attributed to the droplets were noted on an average of 6.7 ± 1.5 days following the injection and followed an average of 10.4 ± 3.75 injections over a period of 3.4 ± 1.9 years and resolved in 5 of our 7 patients within 9 months. CONCLUSIONS AND IMPORTANCE: Symptomatic intravitreal silicone oil droplets are a rare complication of intravitreal injections. Symptoms are generally transient and not clinically significant and hence the benefits of treating potentially blinding eye diseases in this fashion appear to outweigh the limited risk of the rare, temporary floaters. The current series may be related to a batch or batches of syringes.

Combined Scleral Flap with Donor Scleral Patch Graft for Anterior Tube Placement in Glaucoma Drainage Device Surgery.

Purpose. To report a new technique for anterior placement of tubes for glaucoma drainage devices to reduce the risk of tube erosions. Methods. Retrospective review of select cases of Ahmed Valve surgery combined with the novel method of a limbal-based scleral flap covered by a scleral patch graft to cover the tube at the entrance through the limbus. Intraoperative and postoperative illustrations are shown to highlight the method of tube placement. Results. In this retrospective case series, 3 patients are presented illustrating the technique. Two had neovascular glaucoma and one had primary open-angle glaucoma (POAG). On average, intraocular pressure was reduced from 39 ± 14 mmHg to 15 ± 2 mmHg and the number of glaucoma medications was reduced from 4 ± 1 to 0. Preoperative and most recent visual acuities were hand-motion (HM) and HM, 20/60 and 20/50, and 20/70 and 20/30, respectively. Conclusion. The combination of a limbal-based scleral flap with scleral patch graft to cover the tube with glaucoma drainage devices may be an effective means to reduce erosion and protect against endophthalmitis.

Twenty-four-Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes - Protocol 3 with High Dose (READ-3) Study.

PURPOSE: To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). DESIGN: Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. PARTICIPANTS: A total of 152 patients (152 eyes) with DME. METHODS: Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. MAIN OUTCOME MEASURES: The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. RESULTS: A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) (P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P = 0.08). The mean change in CFT was -192.53 µm in the 0.5 mg RBZ group and -170.64 µm in the 2.0 mg RBZ group (P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. CONCLUSIONS: At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

Therapeutic effect of dexamethasone implant in retinal vein occlusions resistant to anti-VEGF therapy.

PURPOSE: To test the efficacy of the intravitreal dexamethasone (DEX) implant in patients with retinal vein occlusions (RVOs) who have failed multiple anti-vascular endothelial growth factor (anti-VEGF) treatments. METHODS: A randomized exploratory study of ten patients with branch RVO or central RVO who received at least two previous anti-VEGF treatments and had persistent or unresponsive cystoid macular edema. Treatment with the DEX implant was either every 4 months or pro re nata (PRN) depending on their group assignment for 1 year. Multifocal electroretinography and microperimetry were the primary end points, with high-resolution optical coherence tomography and best-corrected visual acuity as the secondary end points. RESULTS: All patients in both the every 4 month and PRN cohorts who completed the study received the three maximal injections of DEX; therefore, the data from both cohorts were combined and reported as a case series. On average, the multifocal electroretinography amplitude increased significantly from 5.11±0.66 to 24.19±5.30 nV/deg2 at 12 months (P<0.005), mean macular sensitivity increased from 7.67±2.10 to 8.01±1.98 dB at 4 months (P=0.32), best-corrected visual acuity increased significantly from 51.0±5.1 to 55.4±5.1 early treatment of diabetic retinopathy study letters at 2 months (P<0.05), and central retinal thickness decreased from 427.6±39.5 to 367.1±37.8 µm at 4 months (P<0.05). Intraocular pressure increased significantly in one patient, with that patient requiring an additional glaucoma medication for management. Additionally, cataract progression increased significantly (P<0.05) in this patient population and partially limited analysis of other end points. CONCLUSION: DEX should be considered as a treatment option in patients with RVOs who have failed anti-VEGF therapy, as the results of this study demonstrated an improvement in retinal morphology and macular function. Cataract progression did occur following multiple consecutive injections; however, steroid-induced glaucoma was not a limiting factor.

Strong topical steroid, NSAID, and carbonic anhydrase inhibitor cocktail for treatment of cystoid macular edema.

PURPOSE: To report the combination cocktail of strong steroid, non-steroidal anti-inflammatory drug (NSAID), and carbonic anhydrase inhibitor drops for treatment of cystoid macular edema. METHODS: This is a retrospective case series of patients with cystoid macular edema managed with a topical combination of strong steroid (difluprednate), NSAID, and carbonic anhydrase inhibitor drops. The patients were followed with optical coherence tomography and fluorescein angiography. RESULTS: In our six cases, resolution of the cystic edema with improvement in visual acuity was achieved with the use of a combination cocktail of drops. Leakage on fluorescein angiography and cystic edema on optical coherence tomography both responded to treatment with the topical cocktail of drops. CONCLUSION: A topical cocktail of strong steroid, NSAID, and carbonic anhydrase inhibitor drops are effective for managing cystoid macular edema. Further studies comparing this combination with more invasive treatments should be undertaken to determine the efficacy of this cocktail over other treatment options.

Acute macular edema following intracorporeal prostaglandin injection for erectile dysfunction.

PURPOSE: We aimed to describe the first case of macular edema following intracorporeal injection of alprostadil, a prostaglandin E1. METHODS: This was a retrospective case report followed with optical coherence tomography, fundus photos, and fluorescein angiography images. RESULTS: A patient developed bilateral cystoid macular edema following intracorporeal injection of alprostadil, a prostaglandin E1 for treatment of erectile dysfunction. The edema resolved following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, with subsequent recovery in visual acuity. DISCUSSION: Systemic prostaglandin administration can cause macular edema and vision loss, indicating that elevated systemic prostaglandin levels may affect visual function. This has potential implications for other systemic disorders and treatments that could affect macular function.

Pars plana Ahmed valve and vitrectomy in patients with glaucoma associated with posterior segment disease.

PURPOSE: To assess the safety and efficacy of a modified technique for pars plana placement of the Ahmed valve in combination with pars plana vitrectomy in the treatment of glaucoma associated with posterior segment disease. METHODS: Thirty-nine eyes with glaucoma associated with posterior segment disease underwent pars plana vitrectomy combined with Ahmed valve placement. All valves were placed in the pars plana using a modified technique, without the pars plana clip, and using a scleral patch graft. RESULTS: The 24 eyes diagnosed with neovascular glaucoma had an improvement in intraocular pressure from 37.6 mmHg to 13.8 mmHg and best-corrected visual acuity from 2.13 logarithm of minimum angle of resolution to 1.40 logarithm of minimum angle of resolution. Fifteen eyes diagnosed with steroid-induced glaucoma had an improvement in intraocular pressure from 27.9 mmHg to 14.1 mmHg and best-corrected visual acuity from 1.38 logarithm of minimum angle of resolution to 1.13 logarithm of minimum angle of resolution. Complications included four cases of cystic bleb formation and one case of choroidal detachment and explantation for hypotony. CONCLUSION: Ahmed valve placement through the pars plana during vitrectomy is an effective option for managing complex cases of glaucoma without the use of the pars plana clip.

Recalcitrant macular edema after intravitreal bevacizumab is responsive to an intravitreal dexamethasone implant in retinal vein occlusion.

PURPOSE: To test the efficacy of an intravitreal dexamethasone implant in patients with recalcitrant macular edema secondary to retinal vein occlusion. METHODS: A retrospective chart review was performed for 18 patients with retinal vein occlusion who received multiple bevacizumab intravitreal injections before treatment with an intravitreal dexamethasone implant. RESULTS: Two subgroups of bevacizumab-resistant patients were identified. Both subgroups responded to subsequent treatment with an intravitreal dexamethasone implant with an average reduction in central foveal thickness of 146.8 ± 33.65 µm. A visual acuity improvement of 0.26 ± 0.07 (logarithm of minimal angle of resolution) was also noted. Intraocular pressure increased by an average of 3.33 ± 0.66 mmHg and was managed by 1.0 ± 0.5 topical drops. CONCLUSION: A subset of patients do not have resolution of macular edema after treatment with intravitreal bevacizumab. Such patients may respond to treatment with an intravitreal dexamethasone implant.

Na,K-ATPase inhibition alters tight junction structure and permeability in human retinal pigment epithelial cells.

Na,K-ATPase regulates a variety of transport functions in epithelial cells. In cultures of human retinal pigment epithelial (RPE) cells, inhibition of Na,K-ATPase by ouabain and K(+) depletion decreased transepithelial electrical resistance (TER) and increased permeability of tight junctions to mannitol and inulin. Electrophysiological studies demonstrated that the decrease in TER was due to an increase in paracellular shunt conductance. At the light microscopy level, this increased permeability was not accompanied by changes in the localization of the tight junction proteins ZO-1, occludin, and claudin-3. At the ultrastructural level, increased tight junction permeability correlated with a decrease in tight junction membrane contact points. Decreased tight junction membrane contact points and increased tight junction permeability were reversible in K(+)-repletion experiments. Confocal microscopy revealed that in control cells, Na,K-ATPase was localized at both apical and basolateral plasma membranes. K(+) depletion resulted in a large reduction of apical Na,K-ATPase, and after K(+) repletion the apical Na,K-ATPase recovered to control levels. These results suggest a functional link exists between Na,K-ATPase and tight junction function in human RPE cells.