Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy.

PURPOSE: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA). DESIGN: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration. PARTICIPANTS: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea. METHODS: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly. MAIN OUTCOME MEASURES: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells. RESULTS: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes. CONCLUSIONS: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Similarities in Structure and Function of UDP-Glycosyltransferase Homologs from Human and Plants.

The uridine diphosphate glycosyltransferase (UGT) superfamily plays a key role in the metabolism of xenobiotics and metabolic wastes, which is essential for detoxifying those species. Over the last several decades, a huge effort has been put into studying human and mammalian UGT homologs, but family members in other organisms have been explored much less. Potentially, other UGT homologs can have desirable substrate specificity and biological activities that can be harnessed for detoxification in various medical settings. In this review article, we take a plant UGT homology, UGT71G1, and compare its structural and biochemical properties with the human homologs. These comparisons suggest that even though mammalian and plant UGTs are functional in different environments, they may support similar biochemical activities based on their protein structure and function. The known biological functions of these homologs are discussed so as to provide insights into the use of UGT homologs from other organisms for addressing human diseases related to UGTs.

Discovering New Substrates of a UDP-Glycosyltransferase with a High-Throughput Method.

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC-MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.

Structural and functional insights into iron acquisition from lactoferrin and transferrin in Gram-negative bacterial pathogens.

Iron is an essential element for various lifeforms but is largely insoluble due to the oxygenation of Earth's atmosphere and oceans during the Proterozoic era. Metazoans evolved iron transport glycoproteins, like transferrin (Tf) and lactoferrin (Lf), to keep iron in a non-toxic, usable form, while maintaining a low free iron concentration in the body that is unable to sustain bacterial growth. To survive on the mucosal surfaces of the human respiratory tract where it exclusively resides, the Gram-negative bacterial pathogen Moraxella catarrhalis utilizes surface receptors for acquiring iron directly from human Tf and Lf. The receptors are comprised of a surface lipoprotein to capture iron-loaded Tf or Lf and deliver it to a TonB-dependent transporter (TBDT) for removal of iron and transport across the outer membrane. The subsequent transport of iron into the cell is normally mediated by a periplasmic iron-binding protein and inner membrane transport complex, which has yet to be determined for Moraxella catarrhalis. We identified two potential periplasm to cytoplasm transport systems and performed structural and functional studies with the periplasmic binding proteins (FbpA and AfeA) to evaluate their role. Growth studies with strains deleted in the fbpA or afeA gene demonstrated that FbpA, but not AfeA, was required for growth on human Tf or Lf. The crystal structure of FbpA with bound iron in the open conformation was obtained, identifying three tyrosine ligands that were required for growth on Tf or Lf. Computational modeling of the YfeA homologue, AfeA, revealed conserved residues involved in metal binding.

Identification and Quantification of Micro-Bioplastics in Environmental Samples by Pyrolysis-Gas Chromatography-Mass Spectrometry.

Bioplastics are materials that are biobased and/or biodegradable, but not necessarily both. Concerns about environmental plastic pollution are constantly growing with increasing demand for substituting fossil-based plastics with those made using renewable resource feedstocks. For many conventional bioplastics to completely decompose/degrade, they require specific environmental conditions that are rarely met in natural ecosystems, leading to rapid formation of micro-bioplastics. As global bioplastic production and consumption/use continue to increase, there is growing concern regarding the potential for environmental pollution from micro-bioplastics. However, the actual extent of their environmental occurrence and potential impacts remains unclear, and there is insufficient mass concentration-based quantitative data due to the lack of quantitative analytical methods. This study developed and validated an analytical method coupling pressurized liquid extraction and pyrolysis-gas chromatography-mass spectrometry combined with thermochemolysis to simultaneously identify and quantify five targeted micro-bioplastics (i.e., polylactic acid (PLA), polyhydroxyalkanoate, polybutylene succinate, polycaprolactone, and polybutylene adipate terephthalate (PBAT)) in environmental samples on a polymer-specific mass-based concentration. The recovery of spiked micro-bioplastics in environmental samples (biosolids) ranged from 74 to 116%. The limits of quantification for the target micro-bioplastics were between 0.02 and 0.05 mg/g. PLA and PBAT were commonly detected in wastewater, biosolids, and sediment samples at concentrations between 0.07 and 0.18 mg/g. The presented analytical method enables the accurate identification, quantification, and monitoring of micro-bioplastics in environmental samples. This study quantified five micro-bioplastic types in complex environmental samples for the first time, filling in gaps in our knowledge about bioplastic pollution and providing a useful methodology and important reference data for future research.

Effect of Toxic Phthalate-Based Plasticizer on the Biodegradability of Polyhydroxyalkanoate.

While new biodegradable materials are being rapidly introduced to address plastic pollution, their end-of-life impacts remain unclear. Biodegradable plastics typically comprise a biopolymer matrix with functional additives and/or solid fillers, which may be toxic. Here, using an established method for continuous biodegradation monitoring, we investigated the impact of a commonly used plasticizer, dibutyl phthalate (DBP), on the biodegradation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) in soil. The presence of DBP delayed the initial stage of PHBV biodegradation but then accelerated subsequent rates of biodegradation. Furthermore, it led to significant increases in total bacterial and fungal biomass and altered the composition of microbial communities with significant increases in the relative abundances of Thauera (gammaproteobacterial) and Mucor circinelloides (fungal) populations. It is proposed, with evidence from biodegradation behavior and microbial analysis, that the presence of DBP likely stimulated a microbial community shift, introduced higher proportions of more readily degradable amorphous regions from the plasticizing effect, and facilitated access to the bulk polymer matrix for microorganisms or at least their associated enzymes. These effects in combination overcame the initial inhibition effect of the DBP and resulted in a net increase in the rate of biodegradation of PHBV.

Pneumatic Vitreolysis with Perfluoropropane for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH.

PURPOSE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT (vitreomacular adhesion was ≤3000 µm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (≤250 µm at the narrowest point) and VA of 20/25 to 20/400. METHODS: Pneumatic vitreolysis using perfluoropropane (C3F8) gas. MAIN OUTCOME MEASURES: Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). RESULTS: From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12% [95% CI, 6%-23%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n = 6) or retinal tear (n = 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66% [95% CI, 44%-88%]; P< 0.001). The mean change in VA from baseline at 24 weeks was 6.7 letters in the PVL group and 6.1 letters in the sham group (adjusted difference, -0.8 [95% CI, -6.1 to 4.5]; P = 0.77). In Protocol AH, 10 of 35 eyes (29% [95% CI, 16%-45%]) achieved FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks was -1.5 letters (95% CI, -10.3 to 7.3 letters). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.

Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.

Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information.

Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy.

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and ligand response properties of MphR, which is able to control gene expression in response to a molecular signal in cells. Furthermore, we studied molecular interactions between the TetR DNA-binding module and MphR ligand-binding module by using mutant analysis. Together, we demonstrated that TetR family regulators contain discrete and functional modules that can be used to build biological components with novel properties. This work highlights the utility of rational design as a means of creating modular parts for cell engineering and introduces new possibilities in rewiring cellular response pathways.

Next-generation biocontainment systems for engineered organisms.

The increasing use of engineered organisms for industrial, clinical, and environmental applications poses a growing risk of spreading hazardous biological entities into the environment. To address this biosafety issue, significant effort has been invested in creating ways to confine these organisms and transgenic materials. Emerging technologies in synthetic biology involving genetic circuit engineering, genome editing, and gene expression regulation have led to the development of novel biocontainment systems. In this perspective, we highlight recent advances in biocontainment and suggest a number of approaches for future development, which may be applied to overcome remaining challenges in safeguard implementation.

A retrospective study on risk assessment and management of forensic psychiatric inpatients in Hong Kong.

The Department of Forensic Psychiatry of Castle Peak Hospital is the only facility in Hong Kong that provides territory-wide forensic psychiatric services for patients with criminal involvement. This retrospective study aimed to explore whether the rehabilitation programs provided by the department could significantly reduce the risks of forensic psychiatric inpatients as measured by the Short-Term Assessment of Risk and Treatability (START). START ratings of inpatients who were hospitalized in the department for more than 3 months and were discharged to the community during the period from 11 April 2015 to 31 March 2019 were analyzed. A total of 79 patients were assessed, of whom 61 (77.2%) were males. Fifty-four (68.4%) patients suffered from schizophrenia. START scores upon admission (strength score = 5.67; vulnerability score = 17.43) and upon discharge (strength score = 6.87, vulnerability score = 11.18) indicated significant reduction of risks among inpatients (p < 0.05).

'Deadman' and 'Passcode' microbial kill switches for bacterial containment.

Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism.

Are lactoferrin receptors in Gram-negative bacteria viable vaccine targets?

A number of important Gram-negative pathogens that reside exclusively in the upper respiratory or genitourinary tract of their mammalian host rely on surface receptors that specifically bind host transferrin and lactoferrin as a source of iron for growth. The transferrin receptors have been targeted for vaccine development due to their critical role in acquiring iron during invasive infection and for survival on the mucosal surface. In this study, we focus on the lactoferrin receptors, determining their prevalence in pathogenic bacteria and comparing their prevalence in commensal Neisseria to other surface antigens targeted for vaccines; addressing the issue of a reservoir for vaccine escape and impact of vaccination on the microbiome. Since the selective release of the surface lipoprotein lactoferrin binding protein B by the NalP protease in Neisseria meningitidis argues against its utility as a vaccine target, we evaluated the release of outer membrane vesicles, and transferrin and lactoferrin binding in N. meningitidis and Moraxella catarrhalis. The results indicate that the presence of NalP reduces the binding of transferrin and lactoferrin by cells and native outer membrane vesicles, suggesting that NalP may impact all lipoprotein targets, thus this should not exclude lactoferrin binding protein B as a target.

PNEUMATIC VITREOLYSIS FOR RELIEF OF VITREOMACULAR TRACTION.

PURPOSE: To evaluate the outcome of perfluoropropane (C3F8) gas injection for symptomatic vitreomacular traction (VMT) with or without Stage 2 macular hole (MH). METHODS: A retrospective review of eyes with VMT treated with 0.3 mL of C3F8 gas was performed. Patients avoided the supine position until gas resolution. Patients with small MH maintained partial face-down positioning. RESULTS: Forty-nine consecutive patients (50 eyes) with symptomatic VMT underwent pneumatic vitreolysis between 2010 and 2016. A posterior vitreous detachment developed in 43 eyes (86.0%) after a single gas injection, at a median of 3.0 weeks. Twenty-eight of 35 eyes (80.0%) with VMT only and all 15 eyes (100%) with a small Stage 2 MH developed a posterior vitreous detachment, with MH closure in 10 of 15 eyes (66.7%). Median baseline and last best spectacle-corrected visual acuities were 20/50 and 20/40, respectively (P < 0.001). Mean follow-up time was 11.1 ± 9.9 months. Rate of posterior vitreous detachment was reduced with presence of diabetes mellitus (25%) and with thick cellophane membrane (50%). Univariate analysis showed increased VMT release for eyes with VMT extent within 1 disk area (χ = 13.1, P = 0.002), eyes with absence of diabetes mellitus (χ = 8.8, P = 0.007), and eyes with Stage 2 MH (χ = 5.47, P = 0.019); there was a trend between success and lack of thick cellophane membrane (χ = 3.32, P = 0.068). Results using logistic regression also showed younger age (P = 0.012), followed by better baseline best spectacle-corrected visual acuity (P = 0.044), lack of diabetes mellitus (P = 0.077), and female gender (P = 0.045) to be predictors of increased VMT release. One VMT-only eye formed a MH and another VMT-only eye developed a retinal detachment. Both eyes responded to vitrectomy. CONCLUSION: Pneumatic vitreolysis with limited face-down position is a viable option for treating VMT with few adverse events. More studies are needed to elucidate its indications, benefits, and risks.

Antibiotics induce redox-related physiological alterations as part of their lethality.

Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.

Identification and codon reading properties of 5-cyanomethyl uridine, a new modified nucleoside found in the anticodon wobble position of mutant haloarchaeal isoleucine tRNAs.

Most archaea and bacteria use a modified C in the anticodon wobble position of isoleucine tRNA to base pair with A but not with G of the mRNA. This allows the tRNA to read the isoleucine codon AUA without also reading the methionine codon AUG. To understand why a modified C, and not U or modified U, is used to base pair with A, we mutated the C34 in the anticodon of Haloarcula marismortui isoleucine tRNA (tRNA2(Ile)) to U, expressed the mutant tRNA in Haloferax volcanii, and purified and analyzed the tRNA. Ribosome binding experiments show that although the wild-type tRNA2(Ile) binds exclusively to the isoleucine codon AUA, the mutant tRNA binds not only to AUA but also to AUU, another isoleucine codon, and to AUG, a methionine codon. The G34 to U mutant in the anticodon of another H. marismortui isoleucine tRNA species showed similar codon binding properties. Binding of the mutant tRNA to AUG could lead to misreading of the AUG codon and insertion of isoleucine in place of methionine. This result would explain why most archaea and bacteria do not normally use U or a modified U in the anticodon wobble position of isoleucine tRNA for reading the codon AUA. Biochemical and mass spectrometric analyses of the mutant tRNAs have led to the discovery of a new modified nucleoside, 5-cyanomethyl U in the anticodon wobble position of the mutant tRNAs. 5-Cyanomethyl U is present in total tRNAs from euryarchaea but not in crenarchaea, eubacteria, or eukaryotes.

TYPE 1 VERSUS TYPE 3 NEOVASCULARIZATION IN PIGMENT EPITHELIAL DETACHMENTS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Prospective Study.

PURPOSE: To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. METHODS: In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. RESULTS: Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1-4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1-2) injections (P = 0.0251). CONCLUSION: Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy.

Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes.

Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRNAs representing different classes of critical response proteins. In budding yeast exposed to four oxidants and five alkylating agents, tRNA modification patterns accurately distinguished among chemically similar stressors, with 14 modified ribonucleosides forming the basis for a data-driven model that predicts toxicant chemistry with >80% sensitivity and specificity. tRNA modification subpatterns also distinguish SN1 from SN2 alkylating agents, with SN2-induced increases in m(3)C in tRNA mechanistically linked to selective translation of threonine-rich membrane proteins from genes enriched with ACC and ACT degenerate codons for threonine. These results establish tRNA modifications as predictive biomarkers of exposure and illustrate a novel regulatory mechanism for translational control of cell stress response.

FACTORS INFLUENCING NEED FOR RETREATMENT AND LONG-TERM VISUAL OUTCOME AFTER INTRAVITREAL BEVACIZUMAB FOR MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To evaluate the efficacy and the predictive factors associated with the need for retreatment and long-term visual outcome after intravitreal bevacizumab for myopic choroidal neovascularization (CNV). METHODS: Retrospective cohort study of 93 eyes with subfoveal or juxtafoveal myopic CNV treated initially with either 3-monthly or single intravitreal bevacizumab injections followed by pro re nata retreatment. The efficacy was evaluated by the best-corrected visual acuity (BCVA) during follow-up visits. Backward stepwise multiple linear regression analyses were performed to evaluate the potential predictive factors on final BCVA, change in BCVA, and number of injections. Multiple logistic regression was performed to evaluate the potential predictive factors for retreatment. RESULTS: The mean follow-up duration was 25.12 ± 11.18 (SD) months. The mean logMAR BCVA at baseline was 0.72 ± 0.58 logMAR (20/100 Snellen equivalent) and was maintained at 0.39 ± 0.46 logMAR (20/50 Snellen equivalent) at the last follow-up (P < 0.001). The mean number of injections was 3.53 ± 1.70 (range, 3-10), and a total of 25 eyes (26.9%) received retreatment. Patients who received single loading injection had significantly lower mean total number of injections (1.50 ± 0.73 vs. 3.96 ± 1.53). Both subfoveal and juxtafoveal myopic CNV eyes had significant improvement in BCVA (0.28 ± 0.43 vs. 0.22 ± 0.32 [20/40 vs 20/30 Snellen equivalent], P = 0.506), and juxtafoveal myopic CNV eyes had significantly better BCVA at baseline and at the last follow-up than the subfoveal group. Treatment-naive eyes had significant improvement from baseline BCVA, and the amount of improvement was significantly more than those who received previous photodynamic therapy (0.31 ± 0.43 vs. 0.06 ± 0.11 [20/40 vs 20/25 Snellen equivalent], P < 0.001). Multivariate stepwise regression analysis showed that the baseline CNV size (P < 0.05), baseline BCVA (P < 0.001), and duration of symptoms (P < 0.05) were significant predictive factors for final BCVA, and BCVA improvement. Multiple logistic regression analysis identified that CNV size (P = 0.014) and follow-up duration (P = 0.017) were significant predictive factors for retreatment. No significant association was found for number of injections. CONCLUSION: Intravitreal bevacizumab seems to be an effective treatment for both subfoveal and juxtafoveal myopic CNV in the long term. Patients presented with shorter duration of symptoms and smaller CNV size before treatment as significant prognostic factors that predict better visual outcome. Eyes with longer follow-up duration and larger baseline CNV size may have higher risk for retreatment.

Angle-recession glaucoma: long-term clinical outcomes over a 10-year period in traumatic microhyphema.

This study aims to determine the incidence of angle recession and glaucoma after traumatic microhyphema. Records of all patients treated for traumatic hyphema or microhyphema admitted to a district hospital throughout a 10-year period were retrospectively reviewed. Patients with open-globe injury were excluded. The following clinical features were recorded during patients' initial presentation and follow-up visits: Snellen visual acuity, examination with slit-lamp biomicroscopy, intraocular pressure (IOP), dilated fundoscopic examination, gonioscopic examination and treatment. For patients with IOP > 21 mmHg and requiring glaucoma medications, visual field tests were performed. A total of 97 patients met the study criteria, of which 62 had microhyphema and 35 had gross hyphema. Among the traumatic microhyphema patients, 47 (75.8 %) had angle recession and 4 (6.5 %) had glaucoma with mean follow-up of 49 months (range 6-98 months). A statistically significant association was found between angle recession greater than 180° and the occurrence of glaucoma (p < 0.01). No statistically significant differences were found between groups of patients with microhyphema or gross hyphema regarding the incidence of angle recession and glaucoma. The complications of angle recession and glaucoma in patients after traumatic microhyphema appear similar to those found in patients after gross hyphema.