CENTRAL RETINAL ARTERY OCCLUSION AS PRESENTATION OF BARTONELLA ENDOCARDITIS.

BACKGROUND/PURPOSE: To describe a rare ocular presentation of a systemic illness and the important lifesaving diagnosis made by a complete eye examination. METHODS: The patient was evaluated with a comprehensive ophthalmic examination and followed closely in the outpatient setting with optical coherence tomography, fluorescein angiography, and color fundus photos. RESULTS: A 66-year-old man presented with acute vision loss of the left eye. A complete eye examination revealed that he had a central retinal artery occlusion. Systemic workup revealed that he had a mitral valve vegetation and blood cultures grew Bartonella henselae. His kidney biopsy showed membranoproliferative glomerulonephritis, which is often seen with septic emboli. Furthermore, the patient lacked any ocular inflammatory signs. This constellation of findings was diagnostic for a thromboembolic etiology causing his central retinal artery occlusion. At follow-up, the optical coherence tomography demonstrated inner retinal hyperreflectivity and the fluorescein angiogram showed segmented flow and no neovascularization. On follow-up, the patient had a stable examination with light perception vision and completed antibiotic therapy for bartonella endocarditis. CONCLUSION: The detection of a fatal systemic illness was made promptly with a thorough ocular examination. We highlight the importance of a multidisciplinary approach in making a lifesaving diagnosis.

Fellow-Eye Retinal Detachment Risk as Stratified by Hyaloid Status on OCT.

PURPOSE: To evaluate the risk of a rhegmatogenous retinal detachment (RRD) in the fellow eye using posterior hyaloid status as determined by OCT at the time of initial RRD. DESIGN: Retrospective chart review. PARTICIPANTS: Patients with a diagnosis of RRD. METHODS: Posterior hyaloid status-presence or absence of a posterior vitreous detachment (PVD)-in both eyes at the time of initial RRD was determined by OCT imaging. Baseline characteristics, including lattice degeneration, refractive error, prior ocular laser procedures, lens status, and family history of RRD, were recorded. MAIN OUTCOME MEASURES: The main outcome measures were the development of fellow-eye RRD and the time to fellow-eye RRD. In addition, OCT imaging was used in those fellow eyes with a visible posterior hyaloid to document whether a PVD developed during follow-up and time to such an event. RESULTS: A total of 1049 patients with an RRD were followed up for an average of 5.7 ± 0.3 years. Overall, 153 patients (14.6%) received a diagnosis of bilateral sequential RRD during this follow-up period. OCT images were available for 582 fellow eyes; PVD was noted in 229 fellow eyes (39.3%), and an attached hyaloid was noted in 353 fellow eyes (60.7%). An RRD occurred in 7 fellow eyes (3.1%) with a PVD at presentation. Within the cohort of fellow eyes with an attached hyaloid, 28 eyes (7.9%) demonstrated an RRD during follow-up; however, when evaluating only those in which a PVD developed during follow-up, 23.7% of such eyes were found to have an RRD as well. At the time of PVD development in the fellow eye, an additional 21 eyes (17.8%) were noted to have a retinal tear that was treated without progression to RRD. CONCLUSIONS: OCT imaging of the fellow eye at the time of presentation with an RRD offers a significant amount of information regarding risk stratification for RRD in this eye. Patients noted to have a completely detached posterior hyaloid are at a significantly lower risk of RRD than those with a visible posterior hyaloid, who need to be monitored closely at the time of PVD development. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Identifying rhegmatogenous detachments in bullous retinoschisis with optical coherence tomography studies.

PURPOSE: To demonstrate a novel technique for capturing optical coherence tomography images of peripheral retina and its application in identifying rhegmatogenous retinal detachments within bullous retinoschisis. OBSERVATIONS: We report two patients presenting with bullous retinoschisis noted on clinical examination. After performing optical coherence tomography studies utilizing our image acquisition technique these lesions were found to be associated with rhegmatogenous retinal detachments. Both patients were subsequently treated without further complications. CONCLUSIONS AND IMPORTANCE: The image acquisition technique described herein allows visualization of peripheral retina utilizing optical coherence tomography studies to identify areas of rhegmatogenous retinal detachment within bullous retinoschisis that are otherwise difficult to discern.

Combination verteporfin photodynamic therapy ranibizumab-dexamethasone in choroidal neovascularization due to age-related macular degeneration: results of a phase II randomized trial.

PURPOSE: To assess whether combination therapy (CT) reduces retreatments when compared to ranibizumab monotherapy (RM), while safely maintaining similar vision outcomes. METHODS: In this 24-month trial, patients with age-related macular degeneration (AMD) were randomized to 1) quarter-fluence or 2) half-fluence triple therapy (verteporfin photodynamic therapy [vPDT] + ranibizumab + dexamethasone), 3) half-fluence double therapy (vPDT + ranibizumab), or 4) RM. The primary outcomes were number of retreatment visits and change from baseline in visual acuity (VA) at 12 months. RESULTS: One hundred sixty-two subjects enrolled. There were 4.0 (P=0.02), 3.2 (P<0.001), 4.1 (P=0.03), and 5.7 retreatment visits through month 12, and 5.9 (P=0.03), 4.3 (P<0.001), 5.9 (P=0.02) and 8.7 through month 24, in groups 1, 2, 3, and 4, respectively (P-value comparing with RM). Month 12 VA score change from baseline (95% confidence interval) was +3.6 (-0.9 to +8.1), +6.8 (+2.4 to +11.1), +5.0 (+0.6 to +9.3), and +6.5 (+1.7 to +11.4), respectively. CONCLUSION: CT resulted in significantly fewer retreatment visits than a RM regimen at months 12 and 24. VA results appeared similar although wide confidence intervals preclude conclusions regarding vision outcomes.

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.

Optical coherence tomography difference maps and average macular volume for geographic atrophy.

PURPOSE: To demonstrate the ability to monitor geographic atrophy (GA) volumetrically through all retinal layers with high-resolution optical coherence tomography difference maps and average macular volume. METHODS: Observational case report. RESULTS: Two patients diagnosed with GA were followed up for multiple years with consecutive high-resolution optical coherence tomography studies along with fundus photography and fluorescein angiography or fundus autofluorescence. Difference maps visually reflect macular thinning associated with expansion of GA witnessed on alternative studies. In addition, these maps show progressive macular thinning within previously delineated areas of GA. Average macular volume quantitatively demonstrates the decreasing volume associated with the expanding atrophy. CONCLUSION: Difference maps and average macular volume allow quantitative analysis of GA and may be a useful tool for patient care and clinical trials.

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.