Accuracy of intraocular lens formulas in combined phacovitrectomy.

PURPOSE: To assess the refractive accuracy of eight intraocular lens (IOL) formulas in eyes that underwent combined phacovitrectomy. METHODS: A retrospective chart review of 59 eyes that underwent uncomplicated phacovitrectomy between 2017 and 2020 at the Johns Hopkins Wilmer Eye Institute. Inclusion criteria were postoperative best corrected visual acuity of 20/40 or better within 6 months of surgery and IOL implantation in the capsular bag. The Barrett Universal II (BUII), Emmetropia Verifying Optical (EVOv2.0), Hill-Radial Basis Function (Hill-RBFv3.0), Hoffer Q, Holladay I, Kane, Ladas Super Formula (LSF), and SRK/T formulas were compared for accuracy in predicting postoperative spherical equivalents (SE) using Wilcoxon rank sum tests. Pearson's correlation coefficients were used to assess correlations between biometric parameters and errors for all formulas. RESULTS: Prediction errors of SE ranged from - 1.69 to 1.43 diopters (D), mean absolute errors (MAE) ranged from 0.39 to 0.47 D, and median absolute errors (MedAE) ranged from 0.23 to 0.37 D among all formulas. The BUII had the lowest mean error (- 0.043), MAE (0.39) and MedAE (0.23). The BUII also had the highest percentage of eyes with predicted error within ± 0.25 D (51%) and ± 0.50 D (83%). Based on MedAE however, no pairwise comparisons resulted in statistically significant differences. Axial length (AL) was positively correlated with the error from the Hoffer Q and Holladay I formulas (correlation coefficients = 0.34, 0.30, p values < 0.01, 0.02 respectively). CONCLUSION: While all eight IOL formulas had comparable accuracy in predicting refractive outcomes in eyes undergoing combined phacovitrectomy, the BUII and Kane formulas had a tendency to greater accuracy.

Comparison of simultaneous vs sequential pars plana vitrectomy and cataract surgery.

BACKGROUND: To compare the clinical outcomes of patients undergoing sequential pars plana vitrectomy (PPV) followed by cataract extraction surgery (CE) [PPV/CE], simultaneous PPV and CE (PPV + CE), and sequential CE followed by PPV [CE/PPV]. METHODS: A retrospective observational cohort study of 427 eyes of 404 patients who underwent either sequential or simultaneous PPV and CE surgery between March 2016 and May 2021. Pre-operative and post-operative assessments (up to 2 years of follow-up visits) of uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), spherical equivalent (SEQ), and refractive prediction error (RPE) was done. Main outcome measures were both visual (UCVA, CDVA) and refractive (RPE, SEQ). RESULTS: There was a statistically significant difference in CDVA of the PPV/CE, PPV + CE, CE/PPV groups (logMAR 0.34 ± 0.40, 0.65 ± 0.61, and 0.55 ± 0.60, respectively) at one month postoperatively (POM1) (P < 0.001), and at the POM12 visits (logMAR 0.25 ± 0.34, 0.53 ± 0.68, and 0.44 ± 0.48; P = 0.04). In the subgroup analysis of patients with a diagnosis of either epiretinal membrane or vitreous opacities, there was no statistically significant difference in SEQ (P = 0.09) and RPE (P = 0.13) at the combined 1 month and 3 month visits. CONCLUSION: Simultaneous PPV and cataract surgery demonstrated similar improvements in visual acuity and refractive outcomes, as well as comparable intraoperative and postoperative complication profiles to sequential surgery.

Predictors of intraocular pressure reduction after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a prospective trial.

PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.

Detection of Human Papillomavirus in Squamous Lesions of the Conjunctiva Using RNA and DNA In-Situ Hybridization.

In-situ hybridization provides a convenient and reliable method to detect human papillomavirus (HPV) infection in formalin-fixed paraffin-embedded tissue. Cases of conjunctival papillomas, conjunctival intraepithelial neoplasia (CIN), conjunctival carcinoma in situ (cCIS), and invasive squamous cell carcinoma (SCC), in which low-risk (LR) and/or high-risk (HR) HPV types were evaluated by RNA or DNA in-situ hybridization, were retrospectively identified. LR HPV types were frequently detected in conjunctival papillomas (25/30, 83%), including 17/18 (94%) with RNA probes, compared to 8/12 (75%) with DNA probes. None of the CIN/cCIS or SCC cases were positive for LR HPV by either method. HR HPV was detected by RNA in-situ hybridization in 1/16 (6%) of CIN/cCIS cases and 2/4 (50%) of SCC cases, while DNA in-situ hybridization failed to detect HPV infection in any of the CIN/cCIS lesions. Reactive atypia and dysplasia observed in papillomas was generally associated with the detection of LR HPV types. Collectively, our findings indicate RNA in-situ hybridization may provide a high-sensitivity approach for identifying HPV infection in squamous lesions of the conjunctiva and facilitate the distinction between reactive atypia and true dysplasia. There was no clear association between HPV infection and atopy in papillomas or dysplastic lesions.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study.

PURPOSE: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy.

Diabetic eye disease is the most common cause of severe vision loss in the working-age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In PDR, retinal ischemia leads to the up-regulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization in some, but not all, diabetic patients, implicating additional factor(s) in PDR pathogenesis. Here we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identify angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from PDR patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of PDR and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease.

NSAIDs and Corticosteroids for the Postoperative Management of Age-Related Cataract Surgery: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the safety and efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in the postoperative management of cataract surgery for age-related cataract in adults. DESIGN: Meta-analysis. METHODS: Cochrane, Embase, PubMed, Scopus, Web of Science and CINAHL were searched for articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42022364733). Randomized controlled trials of patients undergoing age-related cataract surgery treated with corticosteroids, NSAIDs, or a combination were included. RESULTS: A total of 19 studies were included, with 3473 patients (3638 eyes) treated following cataract surgery with NSAIDs (n = 1479), corticosteroids (n = 1307), or a combination (n = 687). Combination treatment demonstrated favorable best-corrected visual acuity compared to corticosteroids 4 to 6 weeks postoperatively (MD = -0.01 logMAR, 95% CI: -0.02, -0.01, I2 = 0%). NSAIDs had more favorable flare values than corticosteroids on day 7 (MD = -9.17 photons/ms, 95% CI = -16.52, -1.82, I2 = 94%), day 14 (MD = -5.23 photons/ms, 95% CI = -8.35, -2.11, I2 = 94%), and 4 to 6 weeks (MD = -1.62 photons/ms, 95% CI = -3.03, -0.20, I2 = 93%) postoperatively. Furthermore, 4 to 8 weeks postoperatively, patients treated with NSAIDs showed lower central macular thickness (MD = -13.26 µm, 95% CI = -18.66, -7.86, I2 = 81%) compared to those treated with corticosteroids. NSAIDs and combination treatment were associated with a lower incidence of central macular edema (OR = 0.16, 95% CI = 0.07, 0.35, I2 = 61%; OR = 0.21, 95% CI = 0.10, 0.45, I2 = 31%) than corticosteroids 4 to 8 weeks postoperatively. CONCLUSIONS: NSAIDs and combination treatments could be regarded as more effective and safer alternatives to corticosteroids alone in the postoperative management of cataract surgery. Further studies should be conducted to determine why this evidence has not been reflected in practice patterns, and to further compare the effectiveness of NSAIDs and combination treatments.

Anti-inflammatory medication use after cataract surgery: online survey of practice patterns.

PURPOSE: To determine current prescribing patterns for topical or intraocular/periocular anti-inflammatory medications (AIMs) after routine cataract surgery. SETTING: kera-net online members. DESIGN: Cross-sectional survey. METHODS: An online survey was distributed to subscribers of kera-net, a global online platform sponsored by the Cornea Society. Questions were asked regarding the use of topical or intraocular/periocular AIM after cataract surgery and types of medications prescribed. RESULTS: Of 217 surgeon respondents (23% response rate), 171 (79%) practiced in the United States and 171 (79%) were cornea subspecialists. Most of the respondents (n = 196, 97%) prescribed topical corticosteroids after routine cataract surgery. The most frequently prescribed were prednisolone acetate (n = 162, 83%), followed by dexamethasone (n = 26, 13%), difluprednate (n = 24, 12%), and loteprednol etabonate (n = 13, 7%). Corticosteroids comprised (n = 40, 32%) of total intraocular/periocular injections, with triamcinolone acetonide 10 or 40 mg (n = 19, 47.5%) most commonly used. 23 surgeons (58%) who utilized intraocular/periocular corticosteroids also prescribed topical corticosteroids. Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 148 surgeons (73%). CONCLUSIONS: Most surgeons prescribed topical AIM after routine cataract surgery. Many surgeons injected intraocular or periocular AIM while prescribing topical AIM. The diversity of practice patterns may reflect the lack of clear evidence-based guidelines.

Seidel and India ink tests assessment of different clear cornea side-port incision configurations.

BACKGROUND: Post-cataract endophthalmitis has increased after introduction of clear cornea incisions (CCI). Laboratory models suggested that these incisions might not be competent at certain changes in intraocular pressure (IOP). Considering that side-port incisions (SPI) might behave similarly, the purpose of the present study was to determine the most stable side-port incision configuration. METHODS: Using four cadaveric human eyes, four different side-port incisions (SPI) were created in each cornea: 1.5 mm and 2.5 mm squared tunnel, 1.5 mm and 2.5 mm stab tunnel. Fluorescein was placed on the eye, and the IOP varied from 10 to 80 mmHg. IOP at which each SPI started leaking was recorded. In the second part of the study, India ink was applied to the corneal surface at normal IOP, and then rinsed with balanced salt solution (BSS). The ink influx was recorded by planimetry. IOP was elevated to 80 mmHg, ink was reapplied, and IOP was dropped to 0 mmHg. Ink influx was measured again. Histological examination was used to visualize ink inflow into each incision. RESULTS: There was no statistically significant difference in the IOP levels at which the different incisions leaked (p = 0.52). A significant increase in the length of India ink ingress in all incision types was measured after IOP variation (p < 0.05). The 2.5 mm squared incision showed the least increase in ink inflow in this test. CONCLUSION: All incision types of SPIs tested exhibited similar resistance to leakage after IOP variation. Good resistance to wound leakage may not predict adequate resistance to the inflow of bacterial-sized particles into the wound.

Factors Predictive of Refractive Error After Toric Lens Implantation.

Purpose: To identify factors related to suboptimal refractive outcomes after toric intraocular lens implantation. Patients and Methods: A retrospective case-control chart review of 446 eyes with toric lens insertion by the same surgeon at a university hospital from 2016 to 2020 was conducted. Pre-operative exam findings, biometry, and one month and three month post-operative vision and refraction were noted. Reviewed charts were considered cases if uncorrected distance visual acuity (UDVA) was worse than 20/40, spherical equivalent (SE) >1 diopter (D) off target, or cylinder >1 D off target. Results: Overall, 93.7% (n = 343) of eyes achieved UDVA of 20/40 or better, 92.7% (n = 306) were within 1 D of target SE, and 90.9% (n = 300) were within 1 D of target cylinder. UDVA cases had more eyes with prior LASIK (21.7% vs 7.0%, p = 0.01) and keratoconus (8.7% vs 0.6%, p < 0.001) than controls. More SE cases had prior radial keratotomy (RK) (8.3% vs 0%, p < 0.001) and keratoconus (12.5% vs 0%, p < 0.001) than controls. More cylinder cases had prior LASIK (30.0% vs 8.7%, p < 0.001) and higher mean astigmatism (2.3 vs 1.5 D, p = 0.02) than controls. More cases in all three analyses had higher toric cylinder power (T5-T9) than controls. Age, sex, eye laterality, axial length, anterior chamber depth, lens power, dry eye, anterior basement membrane dystrophy, and Fuchs' endothelial dystrophy differences were not significant. Conclusion: Prior LASIK or RK, keratoconus, and higher astigmatism may increase the chance of a suboptimal outcome.

Distinguishing Glaucoma, Cataract, and Glaucoma Suspect Based on Visual Symptoms.

PRCIS: Cataract, glaucoma, and glaucoma suspect patients report differing visual symptoms. Asking patients about their visual symptoms may provide useful diagnostic information and inform decision-making in patients with comorbid conditions. PURPOSE: To compare visual symptoms in glaucoma, glaucoma suspect (controls), and cataract patients. METHODS: Glaucoma, cataract, and glaucoma suspect patients at Wilmer Eye Institute responded to a questionnaire rating the frequency and severity of 28 symptoms. Univariate and multivariable logistic regression determined the symptoms that best differentiate each disease pair. RESULTS: In all, 257 patients (mean age: 67.4 ± 13.4 y; 57.2% female; 41.2% employed), including 79 glaucoma, 84 cataract, and 94 glaucoma suspect patients, participated. Compared with glaucoma suspects, glaucoma patients were more likely to report poor peripheral vision (OR 11.29, 95% CI: 3.73-34.16), better vision in 1 eye (OR 5.48, 95% CI: 1.33-22.64), and light sensitivity (OR 4.85, 95% CI: 1.78-13.24), explaining 40% of the variance in diagnosis (ie, glaucoma vs. glaucoma suspect). Compared with controls, cataract patients were more likely to report light sensitivity (OR 3.33, 95% CI: 1.56-7.10) and worsening vision (OR 12.20, 95% CI: 5.33-27.89), explaining 26% of the variance in diagnosis (ie, cataract vs. glaucoma suspect). Compared with cataract patients, glaucoma patients were more likely to report poor peripheral vision (OR 7.24, 95% CI: 2.53-20.72) and missing patches (OR 4.91, 95% CI: 1.52-15.84), but less likely to report worsening vision (OR 0.08, 95% CI 0.03-0.22), explaining 33% of the variance in diagnosis (ie, glaucoma vs. cataract). CONCLUSIONS: Visual symptoms distinguish disease state to a moderate degree in glaucoma, cataract, and glaucoma suspect patients. Asking about visual symptoms may serve as a useful diagnostic adjunct and inform decision-making, for example, in glaucoma patients considering cataract surgery.

Outcomes of Secondary Intraocular Lens Implantation and Descemet Stripping Endothelial Keratoplasty-Comparing Staged Versus Combined Surgical Approach.

PURPOSE: The aim of this study was to compare the outcomes of staged versus combined surgical approach for secondary intraocular lens (IOL) implantation and Descemet stripping endothelial keratoplasty (DSEK). METHODS: This is a retrospective review of 124 eyes from 124 patients who underwent either staged or combined secondary IOL implantation in addition to DSEK over a 5-year period at 2 academic tertiary referral centers, between January 1, 2014, and October 1, 2019. Corrected distance visual acuity (CDVA), presence of graft detachment, primary graft failure (PGF), and cystoid macular edema were documented and analyzed. RESULTS: The CDVA for the 1- to 2- month follow-up period was significantly better in the staged group compared with the combined group ( P = 0.011). By the postoperative 6- to 9-month follow-up period, there was no significant difference in the CDVA between the groups ( P = 0.591). There was no significant difference in the incidence of PGF or graft detachment between the 2 groups ( P > 0.05). In addition, there was no significant difference in the CDVA or rate of postoperative complications between the different methods of IOL fixation. CONCLUSIONS: The short-term visual outcomes were significantly better in eyes that underwent staged secondary IOL implantation and DSEK versus the combined surgical approach, although the difference was no longer present at 6 to 9 months. There was no difference in the rate of PGF or graft detachment between the 2 groups.

Treatment of recalcitrant Acanthamoeba Keratitis with Photoactivated Chromophore for Infectious Keratitis Corneal Collagen Cross-Linking (PACK-CXL).

PURPOSE: To describe a case of recalcitrant Acanthamoeba Keratitis (AK) complicated by medical non-compliance and medication intolerance that was successfully treated with photoactivated chromophore for infectious keratitis corneal collagen cross-linking (PACK-CXL). OBSERVATIONS: A 31-year-old male presented with right eye pain and redness in the setting of fresh water exposure and scleral contact lens wear. He had lack of a response to treatment with antiviral therapy for 3 months by an outside provider. Cultures were found to be positive for Acanthamoeba and the patient was treated with an extended course of various anti-amoebic therapies with poor compliance due to pain and toxicity. He was eventually treated with intrastromal voriconazole and Miltefosine without improvement and eventually had PACK-CXL with resolution of his infection and pain. CONCLUSION: PACK-CXL was associated with a dramatic improvement in a case of recalcitrant Acanthamoeba keratitis unresponsive to both traditional and novel therapies and may be a viable alternative or adjunctive therapy for Acanthamoeba keratitis.

In situ transduction of cells in human corneal limbus using adeno-associated viruses: an ex vivo study.

This study aimed to evaluate the efficacy of in situ adeno-associated virus (AAV)-mediated gene delivery into the human corneal limbal region via targeted sub-limbal injection technique. Human cadaveric corneal tissues were fixed on an artificial anterior chamber. Feasibility of sub-limbal injection technique was tested using trypan blue and black India ink. An enhanced green fluorescent protein (eGFP) encoding AAV DJ was injected into sub-limbal region. After AAV injection, corneal tissues were incubated in air-lift culture and prepared for immunohistochemical analysis. Cell survivial and expression of eGFP, stem cell markers (p63α and cytokeratin 19 (KRT19)), and differentiation marker cytokeratin 3 (KRT3) were evaluated using confocal microscopy. Both trypan blue and black India ink stained and were retained sub-limbally establishing specificity of the injection technique. Immunohistochemical analysis of corneas injected with AAV DJ-eGFP indicated that AAV-transduced cells in the limbal region co-express eGFP, p63α, and KRT19 and that these transduced cells were capable of differentiating to KRT3 postitive corneal epithelial cells. Our sub-limbal injection technique can target cells in the human limbus in a reproducible and efficient manner. Thus, we demonstrate that in situ injection of corneal limbus may provide a feasible mode of genetic therapy for corneal disorders with an epithelial etiology.

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization.

Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy.

BackgroundTo reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear.MethodsEyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients' response to treatment.ResultsAt the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients' response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV.FundingThis work was supported by the National Eye Institute, National Institutes of Health grants R01EY029750, R01EY025705, and R01 EY27961; the Research to Prevent Blindness, Inc.; the Alcon Research Institute; and Johns Hopkins University through the Robert Bond Welch and Branna and Irving Sisenwein professorships in ophthalmology.ConclusionAqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.

Breastfeeding and Maternal Age-Related Cataract in the U.S. Population.

PURPOSE: An estimated 38 million and 50 million individuals will have cataract in the U.S. alone by 2030 and 2050, respectively. Breastfeeding is known to improve a number of health outcomes in both breastfed children and breastfeeding mothers. However, little is known about the relationship between breastfeeding and cataract, the leading cause of blindness worldwide, in breastfeeding mothers. This study was conducted to investigate the relationship between breastfeeding and maternal cataract extraction history in a nationally representative sample of the U.S. population. METHODS: A 10-year multistage, probability-sampling survey data was used to identify parous women aged ≥50 years who provided breastfeeding history and cataract extraction history (n = 4897). Breastfeeding history was considered positive if a participant reported breastfeeding at least one child for ≥1 month. The main outcome was cataract extraction history. Estimates are presented in odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: Approximately half of the studied women breastfed at least one child ≥1 month, and about 18% reported cataract extraction history. Participants with a positive breastfeeding history were less likely to have a positive cataract extraction history in both age-adjusted (OR = 0.814, 95%CI = 0.670-0.989) and multivariable logistic regression (OR = 0.794, 95%CI = 0.639-0.988). Higher number of breastfed children was also associated with a lower risk of cataract extraction history (OR = 0.934, 95%CI = 0.883-0.988). CONCLUSIONS: The findings suggest that breastfeeding may be associated with a decrease in the likelihood of age-related cataract extraction in parous women from the U.S. population.

Cataract surgery in Fuchs corneal dystrophy.

PURPOSE OF REVIEW: Patients with decreased vision due to Fuchs corneal dystrophy and cataract can present with a number of challenges to determine the best surgical option for restoring sight. The ophthalmologist must first distinguish how much of the vision loss is due to the cataract versus the Fuchs corneal dystrophy (FCD) before determining the best surgical course, either cataract surgery alone or cataract surgery combined with full thickness or lamellar keratoplasty. This review will discuss the various techniques and clinical signs to ascertain the source of vision loss and how to use this clinical information to help guide the surgical decision making process in order to optimize the best possible outcome. RECENT FINDINGS: Over the last several years, the technique of endothelial keratoplasty has evolved to become an important alternative in the treatment of FCD. Anticipating the correct intraocular lens power for a patient undergoing cataract surgery alone followed by Descemet stripping endothelial keratoplasty (DSEK) or combined cataract surgery with DSEK requires understanding the hyperopic shift that can occur with DSEK and incorporating this correction preoperatively in the intraocular lens power selection. SUMMARY: New developments in the surgical treatment of Fuchs corneal dystrophy have greatly enhanced our ability to restore vision and reduce the dependence on contact lenses in this genetic disease.

Corneoscleral xanthogranuloma treated with chemotherapy: The room for nonsurgical management.

PURPOSE: To describe a clinical case of corneoscleral xanthogranuloma, a rare manifestation of juvenile xanthogranuloma, and xanthoma disseminatum, which responded well to chemotherapy. METHODS: Interventional case report and literature search. RESULTS: A 9-year-old female patient with a disseminated disease showed complete regression of her corneoscleral xanthogranuloma with methotrexate and azathioprine therapy. CONCLUSION: Since they are potentially blinding, corneoscleral xanthogranulomas are commonly surgically excised. While surgical resection has been widely advocated in the literature, immunosuppressive therapy alone may be a pertinent management line of corneoscleral xanthogranuloma, especially with systemic involvement.