Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN COATS DISEASE.

PURPOSE: To evaluate microstructural retinal abnormalities on spectral domain optical coherence tomography (SD-OCT) imaging of eyes with Coats disease. METHODS: This is a multicenter, retrospective study in which SD-OCT images of patients with treatment-naive Coats disease were correlated with clinical examination and visual acuity and, when available, followed longitudinally over time. RESULTS: Macular SD-OCT of 27 eyes with Coats disease revealed intraretinal edema (59%), intraretinal exudates (67%), subretinal fluid (37%), subretinal exudate (48%), ellipsoid zone disruption (52%), external limiting membrane disruption (41%), and subfoveal nodule (26%). All these microstructural abnormalities correlated with worse baseline and final visual acuities (P < 0.05) on univariate analysis, except for intraretinal edema which exhibited a nonstatistically significant trend toward worse baseline visual acuity (P = 0.16). Within stage 2b eyes, external limiting membrane disruption and subretinal nodule on SD-OCT were associated with worse baseline visual acuity (P = 0.02 for both), and there was a trend toward worse final visual acuity with external limiting membrane disruption and subretinal nodule (P = 0.17 for both) and worse baseline (P = 0.08) and final (P = 0.13) visual acuities with ellipsoid zone disruption. No microstructural abnormalities were noted on OCT of fellow eyes. CONCLUSION: Spectral domain OCT can identify microstructural abnormalities in Coats disease that are associated on univariate analysis with worse baseline visual acuity and visual prognosis. Further larger studies are necessary.

Congenital anomalies of the optic disc: insights from optical coherence tomography imaging.

PURPOSE OF REVIEW: Congenital anomalies of the optic nerve are rare but significant causes of visual dysfunction in children and adults. Accurate diagnosis is dependent on a thorough funduscopic examination, but can be enhanced by imaging information garnered from optical coherence tomography (OCT). We review common congenital optic nerve anomalies, including optic disc pit, optic nerve coloboma, morning glory disc anomaly, and hypoplasia of the optic nerve, review their systemic associations, and discuss insights from OCT imaging. RECENT FINDINGS: Optic disc pits are a result of a defect in the lamina cribrosa and abnormal vitreomacular adhesions have been shown to cause maculopathy. In patients with optic nerve colobomas, OCT can be instrumental in diagnosing choroidal neovascularization, a rare but visually devastating complication. The pathogenesis of morning glory disc anomaly has been more clearly elucidated by OCT as occurring from a secondary postnatal mesenchymal abnormality rather than only the initial neuroectodermal dysgenesis of the terminal optic stalk in isolation. OCT studies of optic nerve hypoplasia have demonstrated significant thinning of the inner and outer retinal layers of the perifoveal region and thicker layers in the fovea itself, resulting in a foveal hypoplasia-like pathology, that is, significantly correlated to poorer visual outcomes. SUMMARY: OCT provides detailed in-vivo analysis of these anatomic anomalies and their resulting pathologies, shedding new insights on the pathogenesis, diagnosis, and potential visual outcomes of these conditions in children. Further study employing OCT to elucidate structure-function relationships of congenital optic nerve anomalies will help expand the role of OCT in clinical practice related to diagnosis, prognosis, and management of these entities.

ONE-YEAR OUTCOMES OF A NOVEL TECHNIQUE FOR RESCUING AND SCLERAL FIXATING A POSTERIOR DISLOCATED INTRAOCULAR LENS-BAG COMPLEX WITHOUT CONJUNCTIVAL OPENING (HOFFMAN POCKETS).

PURPOSE: To present the 1-year follow-up of a novel surgical technique that allows for suture fixation of a posteriorly dislocated lens-bag complex without the need for conjunctival incision. METHODS: A retrospective chart review of 19 patients who underwent posterior chamber intraocular lens rescue using the novel surgical technique was performed. Data were collected 1 year after surgery for all patients. RESULTS: Average preoperative vision was 20/500, whereas 3 months and 12 months postoperatively, the vision was 20/65 and 20/54, respectively. Three of 15 eyes had decentration of the sutured intraocular lens, 2 of which required additional surgical repair. CONCLUSION: Outcome data at 1 year support this novel technique as a viable option for the surgical repair of a dislocated lens-capsular bag complex.

BILATERAL SEROUS RETINAL DETACHMENTS IN A PATIENT WITH PREECLAMPSIA WITHOUT HYPERTENSION.

PURPOSE: To report a case of bilateral serous retinal detachments in a patient with preeclampsia without hypertension using multimodal ophthalmic imaging. METHODS: Case report. RESULTS: This case demonstrates the rare presentation of bilateral serous retinal detachment in a patient with preeclampsia without hypertension. Characteristic subretinal fluid was seen on examination and optical coherence tomography. No leakage was noted on fluorescein angiography. Treatment was deferred, and the subretinal fluid resolved within 3 weeks. CONCLUSION: Practitioners should be aware of the rare presentation of serous retinal detachments in preeclampsia, even in the absence of hypertension. Long-term sequelae are uncommon and usually only seen in severe disease. Delivery should be considered once serous retinal detachment develops.

West Nile Virus Chorioretinitis in the Presence of Negative Cerebrospinal Fluid Polymerase Chain Reaction Results.

Purpose: This work aims to evaluate the utility of nucleic acid amplification testing (NAAT) and serology in confirming West Nile Virus (WNV) infection in patients with suspected WNV chorioretinitis. Methods: A retrospective cross-sectional study was conducted of a cluster of patients who presented to the Retina Service of Massachusetts Eye and Ear between September and October 2018. Results: Three patients were identified with classic WNV chorioretinitis lesions with negative cerebrospinal fluid NAAT and positive serum serology findings. The diagnosis of WNV chorioretinitis was made based on the appearance of the fundus lesions and the presence of characteristic findings on fluorescein angiography as previously described in the literature. Conclusions: This report highlights 3 unique cases of WNV chorioretinitis in which NAAT of cerebrospinal fluid failed to identify WNV as the inciting agent. These cases stress the importance of serum serologic testing in diagnosing WNV infection.

Utilization trends of an ophthalmology-specific emergency department: the Massachusetts Eye and Ear experience.

PURPOSE: To describe the utilization trends of a dedicated ophthalmology emergency department (ED) in Boston, Massachusetts. METHODS: The medical records of 500 randomly selected patients who presented at the Massachusetts Eye and Ear (MEE) Emergency Department (ED) from January 2015 to March 2016 were reviewed retrospectively. Data were analyzed using the Pearson χ2 test and multiple logistic regression. The primary study outcome measure was whether a patient's visit was emergent or nonemergent. Emergent or nonemergent conditions were classified based on the diagnosis and treatment required at follow-up appointments. Nonemergent diagnoses were classified as conditions that could have been seen as an outpatient without negative consequences for vision. RESULTS: Of the 500 cases, 252 were males and 248 were females. The median age was 45 years (range, 2-101 years). The most common diagnoses were posterior vitreous detachment (8.6%), corneal abrasion (8.4%), dry eye syndrome (7%), and viral conjunctivitis (5.4%). Of the total, 92.6% of patients originated from within Massachusetts. The majority of patients were self-referred (78.6%) or referred from another hospital (12.8%). Nonemergent visits accounted for 49.4% of patients seen. Compared to patients who presented with duration of symptoms for ≥1 week, patients who presented with symptoms of <1 week were more likely to present with an emergent condition (8.8% vs 41.8%). Referrals from an outside ophthalmologist or hospital were predictive of emergent patient visits (OR, resp., 1.971 [95% CI, 0.478-3.462; P = 0.01]; 1.040 [95% CI, 0.462-1.616; P < 0.001]). CONCLUSIONS: In our study, nonemergent patient visits comprised nearly half of all ophthalmology ED visits. Emergent visits were associated with acute symptoms and referrals from outside healthcare providers.

Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography.

PURPOSE: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). METHODS: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. RESULTS: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of I to 10 years. CONCLUSIONS: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.

Efficacy of Retinal Lesion Screening in Von Hippel-Lindau Patients With Widefield Color Fundus Imaging Versus Widefield FA.

BACKGROUND AND OBJECTIVE: Retinal hemangioblastoma is a retinal tumor in patients with Von Hippel-Lindau (VHL). The authors' objective was to determine whether widefield fluorescein angiography (FA) improves lesion detection. PATIENTS AND METHODS: Retrospective case series of VHL patients who underwent widefield fundus imaging and FA. Masked retina specialists graded fundus images as having: 1) definite retinal hemangioblastoma; 2) possible lesion; 3) no lesion. The number of lesions on FA was compared to widefield color imaging. RESULTS: One hundred six eyes of 55 patients were evaluated. A total of 94 lesions were identified on FA in 61.8% patients. Forty-three lesions (45.7%) were not identified on fundus images. Small lesion detection was significantly higher with FA compared to color imaging (P = .013). CONCLUSIONS: This study reports on improved detection of retinal hemangioblastomas with widefield FA compared to widefield fundus images. The authors recommend VHL monitoring guidelines to include periodic widefield FA to adequately screen for smaller lesions. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e260-e265.].

A Comprehensive Surgical Curriculum Reduced Intra-operative Complication Rates of Resident-performed Cataract Surgeries.

OBJECTIVES: To evaluate the impact of a comprehensive cataract surgery curriculum on the incidence of intraoperative complications. DESIGN: We retrospectively compared the total number of cataract surgeries that the residents performed in all of the teaching sites, and the incidences of intraoperative complications (anterior capsule tear, posterior capsule rent, vitreous loss, anterior vitrectomy, zonular dialysis, iris trauma, hemorrhage, dropped lens fragment, corneal wound burn, incorrect intraocular lens) for the surgeries performed at Massachusetts Eye & Ear by residents in the pre-intervention group (residents graduating in 2004 and 2005), before the implementation of a surgical curriculum, and the residents in the post-intervention group (residents graduating in 2014 and 2015). SETTING: Ophthalmology residency program at a major academic institution. PARTICIPANTS: Residents graduating in 2004, 2005, 2014, and 2015. RESULTS: We reviewed 4373 charts. 2086 of those surgeries were performed at Massachusetts Eye & Ear. The incidence of posterior capsule rent/vitreous loss/anterior vitrectomy was lower in the post-intervention group (1.4% versus 7.7%, p < 0.0001). Other complications were also lower in the post-intervention group. CONCLUSIONS: Implementation of a comprehensive cataract surgery curriculum focusing on pre-operative, intra-operative and post-operative interventions, with an emphasis on patient outcomes resulted in a decrease in the rate of intraoperative complications.

Longitudinal Examination of Fellow-Eye Vascular Anomalies in Coats' Disease With Widefield Fluorescein Angiography: A Multicenter Study.

BACKGROUND AND OBJECTIVE: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time. PATIENTS AND METHODS: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease. RESULTS: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16). CONCLUSIONS: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:221-227.].

The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab.

PURPOSE: To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. DESIGN: Multicenter retrospective cohort study. METHODS: All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. RESULTS: A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. CONCLUSION: In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes.

Prosthetic Replacement of the Ocular Surface Ecosystem Treatment of Ocular Surface Disease After Skull Base Tumor Resection.

BACKGROUND: Prosthetic replacement of the ocular surface ecosystem (PROSE) treatment is an effective, nonsurgical therapeutic option for patients with ocular surface disease related to cranial nerve deficits secondary to skull base tumor resection. METHODS: This case series describes the impact of PROSE treatment in patients with symptomatic exposure keratopathy or neurotrophic keratitis after skull base tumor surgery. RESULTS: All patients improved symptomatically and functionally with PROSE treatment, and have had sustained improvement for as long as 3 years. CONCLUSIONS: In postneurosurgical cases in which neurologic function may recover, PROSE treatment offers a safe, nonsurgical treatment option to support the ocular surface during the period of observation awaiting neurologic recovery.

Current Practice Patterns for Treatment of Retinopathy of Prematurity.

UNLABELLED: To evaluate current practice patterns for the treatment of retinopathy of prematurity (ROP) and characterize factors influencing clinical decisions, a database of all ophthalmologists subspecializing in pediatrics and retina was compiled from membership directories of subspecialty societies and academic institutions in the United States. A web-based survey was emailed to these subspecialists to obtain information regarding demographics, treatment practices, and preferences in hypothetical clinical scenarios. From 2,977 retina and pediatric ophthalmology subspecialists surveyed, 302 self-reported as treating ROP, of whom 56% reported having performed intra-vitreal anti-VEGF injection for ROP. Anti-vascular endothelial growth factor (VEGF) injection was the initial treatment for posterior type 1 high risk ROP preferred by the majority of surveyed ROP treaters, whereas 66% reported uncertainty regarding long-term side effects as the largest barrier to its use. Geographic practice location was associated with anti-VEGF use (P = .019). Anti-VEGF injection as ROP therapy was preferred in some scenarios in our sample. Concerns regarding potential anti-VEGF side effects warrant further investigation. CLINICAL IMPLICATIONS: Intravitreal anti-VEGF injection was chosen as the initial therapeutic option by the majority of ROP treatment providers for posterior type 1 ROP in this survey that assessed treatment preferences for a range of clinical scenarios. Uncertainty regarding long-term side effects was the largest reported barrier to use of anti-VEGF for ROP treatment. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:491-495.].

Post-Marketing Survey of Adverse Events Following Ocriplasmin.

BACKGROUND AND OBJECTIVE: To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. STUDY DESIGN/MATERIALS AND METHODS: Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. RESULTS: There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). CONCLUSION: Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin.

Retina specialists treating cystoid macular oedema secondary to retinal vein occlusion recommend different treatments for patients than they would choose for themselves.

AIMS: To evaluate the presence of cognitive bias among retinal specialists when recommending treatment options for cystoid macular oedema (CMO) secondary to retinal vein occlusion (RVO). METHODS: Two randomly chosen samples of retina specialists were surveyed regarding their treatment and dosing regimen choices among three antivascular endothelial growth factor (anti-VEGF) biologics (aflibercept, bevacizumab and ranibizumab), intravitreal steroid, focal laser and observation for the treatment of CMO secondary to RVO. The first group was asked to make recommendations for two hypothetical patients: one with CMO secondary to branch RVO (BRVO) and the second with CMO secondary to central RVO (CRVO). The second group was asked to make recommendations as if they themselves were the hypothetical patient with the same disease processes. RESULTS: The survey was completed by 492 respondents (20.1%). When comparing anti-VEGF agents for patients with BRVO, a majority of physicians recommended bevacizumab (60.5%) over ranibizumab (37.8%) and aflibercept (1.7%; p<0.0001). For themselves, physicians were more likely to recommend ranibizumab (44.9%) over bevacizumab (39.2%) and aflibercept (15.9%; p<0.0001). When comparing among the anti-VEGF agents chosen for patients with CRVO, a majority of physicians recommended bevacizumab (56.7%) over ranibizumab (28.2%) and aflibercept (15.1%; p<0.0001), but when choosing for themselves, retina specialists were equally divided among the three biologics (aflibercept 30.6%, bevacizumab 36.5% and ranibizumab 32.9%; p=0.559). The results were influenced by geographical location but not by the gender, the length of practice or the type of practice. CONCLUSIONS: Physicians should be aware that cognitive biases exist and take this into consideration when making treatment recommendations for their patients.

Retina Specialists Treating Diabetic Macular Edema Recommend Different Approaches for Patients Than They Would Choose for Themselves.

BACKGROUND AND OBJECTIVE: Prior investigation shows retina specialists may select different treatment for age-related macular degeneration for themselves than for a hypothetical patient. The authors sought to investigate whether a similar bias exists for treatment decisions by retina specialists with regard to diabetic macular edema (DME). PATIENTS AND METHODS: Two surveys asked retina specialists to select treatment for hypothetical patients with DME or for themselves. In Survey 2, a distinction was drawn between a visual acuity (VA) of 20/40 or better and 20/50 or worse. RESULTS: In Survey 1, 54% to 61% of respondents selected bevacizumab (Avastin; Genentech, South San Francisco, CA) for patients and 36% to 40% selected the drug for themselves (P < .0004). It was found that 14% to 17% selected aflibercept (Eylea; Regeneron, Tarrytown, NY) for patients versus 31% to 38% who selected it for themselves (P < .0001). For a VA of 20/40 or better, 42% to 50% selected bevacizumab for their patients versus 32% to 39% (P < .0005) for themselves, and 20% to 23% selected aflibercept for patients versus 39% to 48% (P < .0007) for themselves. For a VA of 20/50 or worse, 24% to 28% chose bevacizumab for patients versus 17% to 20% for themselves (P value was not significant), and 59% to 66% selected aflibercept for their patients versus 66% to 78% for themselves (P < .05). CONCLUSION: Physicians recommend different treatment for their patients than for themselves, though not for a VA of 20/50 or worse, where data support the use of aflibercept over bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:544-554.].