Ultrasound-Guided Pars Plana Vitrectomy.

PURPOSE: To assess the feasibility of a novel surgical technique that combines B-scan ultrasound with modern vitrectomy techniques. METHODS: Patients with a clinical diagnosis of infectious keratitis endophthalmitis, which were scheduled for pars plana vitrectomy and ruled out as candidates for transient keratoprosthesis, were enrolled. The ultrasound probe was placed over the eye to use the images to witness the vitreous movement around the cutter and to establish its position in relation to the retinal wall. The procedure was performed in at least four ultrasound projections (longitudinal-9,6, 3, and 12). All patients were followed for three months, and in each visit, the visual acuity and the presence of adverse effects were assessed. RESULTS: Overall, 12 patients (mean age: 56.2 ± 18.4 years) were enrolled. Visual acuity at baseline was 2.3 ± 0.25 logarithm of the minimum angle of resolution. Sixty-six percent achieved inactivation of endophthalmitis. Two patients had evisceration caused by uncontrolled infection, and two more had retinal detachment during follow-up. Visual acuity at the end of follow-up was 2.1 ± 0.3 logarithm of the minimum angle of resolution ( P = 0.5). CONCLUSION: Ultrasound-guided vitrectomy is a feasible surgical technique. More studies are needed to assess its safety profile and optimize outcomes.

ALTERNATIVE INTRAVITREAL ANTIBIOTICS: A Systematic Review for Consideration in Recalcitrant or Resistant Endophthalmitis.

PURPOSE: To organize, categorize, and create a quick reference guide for the use of intravitreal antibiotic alternatives to the standard combination of vancomycin and ceftazidime for the treatment of endophthalmitis. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The authors searched for all available information regarding intravitreal antibiotics in the last 21 years. Manuscripts were selected according to relevance, level of information, and the available data regarding intravitreal dose, potential adverse effects, bacterial coverage, and relevant pharmacokinetic information. RESULTS: The authors included 164 of 1810 manuscripts. The antibiotics were classified according to their class into fluoroquinolones, cephalosporins, glycopeptide and lipopeptide, penicillins and beta-lactams, tetracyclines, and miscellaneous. The authors also included information regarding intravitreal adjuvants for the treatment of endophthalmitis and one ocular antiseptic. CONCLUSION: The treatment of infectious endophthalmitis is a therapeutic challenge. The current review summarizes the properties of possible intravitreal antibiotic alternatives that should be considered in cases of suboptimal response to initial treatment.

Bioceramic implant reduces intraocular VEGF levels.

Elevated intraocular levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF) have been implicated the development of diabetic retinopathy. Over a decade of clinical evidence shows intravitreal injection of anti-VEGF agents is associated with decreased disease progression and preservation of vision. However, the treatment burden associated with monthly injections limits the effectiveness of existing anti-VEGF therapies. Current research has focused on sustained treatment paradigms such as longer acting drugs, drug delivery implants, and gene therapy. In this study, we tested a novel approach by dialyzing proteins from the vitreous using bioceramic implant composed of hydroxyapatite. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for VEGF absorption. After three months implantation in New Zealand White Cross rabbits, the hydroxyapatite demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged VEGF suppression intraocularly may be accomplished with a bioceramic implant.

Vitreous protein binding with nanopore dialysis membrane device.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the industrialized world, affecting over 8 million patients in the United State alone. While the wet (exudative) form of the disease is treated with intraocular injections, there are currently no approved therapies available for the dry (non-exudative) form of the disease which often affects both eyes in patients with AMD. Current research has focused on developing drugs that can be injected into the eye, but the treatment burden associated with monthly injections limits the effectiveness of this approach. Hence, there is a pressing need for a long-term therapeutic solution for patients suffering from this blinding disease. We detail a novel implantable intraocular device, which adsorbs and traps complement factors associated with AMD. In this study, we tested a novel approach by dialyzing proteins from the vitreous using biocompatible implants composed of a nanopore polyacrylonitrile polymer membrane. Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for complement protein absorption. After a three-month implantation in New Zealand White Cross rabbits, the implant demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology. These studies demonstrate that prolonged CF suppression intraocularly may be accomplished with a nanopore polymer membrane.

Anti-VEGF treatment switch in neovascular age-related macular degeneration: a comparison of aflibercept versus ranibizumab after a single-dose switch.

PURPOSE: To determine the effect achieved from a single dose of anti-VEGF treatment switch, in patients with nAMD previously treated with bevacizumab, switched to either aflibercept or ranibizumab, and to compare the response between aflibercept and ranibizumab. METHODS: In retrospective, observational, and comparative study, patients were divided into two groups: Group 1, patients switched to aflibercept; Group 2, patients switched to ranibizumab. Paired samples t test was performed to measure differences in central macular thickness (CMT). To compare whether there were differences between groups mixed-design ANOVA was used. RESULTS: In Group 1, CMT changed from 360.51 to 260.16 µm, presenting a significant mean difference from PreSwitch to PostSwitch of 100.34 µm (p = 0.002, paired samples t test). In Group 2, CMT changed from 366.33 to 260.72 µm, showing a significant difference from PreSwitch to PostSwitch of 105.61 µm (p ≤ 0.000, paired samples t test). The mixed-design ANOVA compared both groups and resulted in a nonsignificant value of 0.90. CONCLUSION: The effect achieved from a single dose in patients switched to aflibercept or ranibizumab reduced significantly CMT measurements. Comparing aflibercept and ranibizumab, the effect appears to be similar in both drugs, in terms of reduction of CMT.

Progression of gyrate atrophy measured with ultra-wide-field imaging.

The study aims to determine the progression of gyrate atrophy by measuring the area growth of chorioretinal atrophic lesions using ultra-wide-field images (UWFI). A retrospective, observational, and comparative study was conducted and UWFI (200°) were obtained from two patients with gyrate atrophy at baseline and follow-up. Measurements of atrophy were obtained for three types of lesions: Solitary atrophic lesions (SAL), De novo solitary lesions (DNSL), and peripapillary atrophy (PPA). Comparison of baseline and follow-up was done using t tests. Two patients with gyrate atrophy were included. Patient 1 presented 16 SAL, 5 DNSL, and PPA measured for both eyes (BE). Overall area growth (OAG) for SAL (expressed in decimals) presented a mean of 3.41, σ 3.07. DNSL area for BE presented a mean of 1586.08 P (2), σ 1069.55. OAG for PPA presented a mean of 1.21, σ 0.17. Patient 2 presented 5 SAL, no DNSL, and PPA was measured for BE. OAG for SAL presented a mean of 1.58, σ 1.05 (range 1.02-3.47). OAG for PPA presented a mean of 1.05, σ 0.001. Gyrate atrophy progression can be determined by measuring the changes in area using UWFI.

A nanopore membrane regulator device for laser modulated flow after glaucoma surgery.

Glaucoma, the second most common cause of blindness in the world, is a multifactorial disease with several risk factors, of which intraocular pressure (IOP) is a primary contributing factor. Filtration surgery is one of the most effective means to significantly lower IOP compared to medical or laser treatments, and it is typically reserved for advanced disease. However, there are high rates of postoperative complications associated with the procedure, often from over- or under-filtration. To address these problems, the glaucoma drainage device regulator (GDDR) implant was developed to allow post-operative control of aqueous flow and IOP. The device, a tube with a nanopore membrane, is placed beneath the scleral flap. Postoperatively, the membrane surface can be ruptured with a laser to augment flow through the system. This feature allows adjustable control of aqueous flow and diminishes the risk of hypotony in the early postoperative period.

Identification and biometry of horizontal extraocular muscle tendons using optical coherence tomography.

PURPOSE: To purpose if this study was to determine whether the horizontal rectus muscle tendons (HRMTs) can be observed using anterior segment optical coherence tomography (AS-OCT) and to determine the repeatability of its measurements. Also, this study aimed to observe and measure the different external ocular structures at the level of the horizontal rectus muscle (HRM) insertion. METHODS: This was a retrospective, observational, descriptive and comparative study. Images were obtained utilizing the RTVue 100 CAM system. Eyes were analyzed at the three and nine o'clock position. Scans were performed for three different locations: the limbus, the ciliary body and the equator. All scans were analyzed by two graders, separately and blinded. Measurements were performed for: HRMT length; HRM thickness; conjunctival epithelium thickness; conjunctiva and Tenon's capsule thickness; scleral thickness; and external ocular thickness. RESULTS: Results were obtained from twenty eyes of ten volunteers. The conjunctival epithelium thickness was 52.33 µm, the total conjunctiva/Tenon's capsule thickness was 313.54 µm, the medial rectus (MR) thickness was 136.63 µm and the lateral rectus (LR) thickness was 181.65 µm. The MR tendon length was 1,426.88 µm, the LR tendon length was 1,433.65 µm, the scleral thickness was 489.91 µm and the total external ocular structure thickness was 785.17 µm. Intra-observer reproducibility (intraclass correlation coefficient [ICC]) for tendon length was 0.993 for grader #1, 0.989 for grader #2; the muscle thickness ICC was 0.990 for grader #1 and 0.981 for grader #2. The inter-observer reproducibility ICC for tendon length was 0.557; the ICC for muscle thickness was 0.834. CONCLUSIONS: It is possible to visualize and measure HRMTs using AS-OCT. Measurements of the HRM, as well as the surrounding external ocular tissues, can be achieved.

Spectral domain optical coherence tomographic analysis of healthy retina in branch retinal vein occlusion and its response to antiangiogenic therapy.

PURPOSE: To propose a model that measures the effect of intravitreal bevacizumab (IVB) on relatively healthy retina. The purpose is to analyze the remote effect of a branch retinal vein occlusion in the healthy retina, to determine the response it may have to IVB, and to determine if IVB has an atrophic effect on the healthy retina. METHODS: Retrospective, longitudinal comparative analysis of patients with branch retinal vein occlusion treated with IVB. Eyes were divided into experimental (branch retinal vein occlusion eye) and control (contralateral eye) groups. Each eye was analyzed for thickness and area. Thickness measurements were performed for total retinal thickness, inner retina thickness, and outer retina thickness. Area was measured for photoreceptors, choroid, and total retina. RESULTS: Eighteen eyes of 9 patients. For thickness analysis, 1,050 scans were studied, and 126 measurements were performed on 42 scans for area analysis. No difference was observed for thickness, except for inner retina thickness. No difference was observed for area. No difference was observed when analyzing a cumulative exposure to IVB. CONCLUSION: There is no evidence to suggest an atrophic effect caused by IVB when analyzing thickness or area in this experiment. This model could be used to analyze the long-term safety of IVB in larger studies.

Current knowledge and trends in age-related macular degeneration: genetics, epidemiology, and prevention.

PURPOSE: To address the most dynamic and current issues concerning human genetics, risk factors, pharmacoeconomics, and prevention regarding age-related macular degeneration. METHODS: An online review of the database Pubmed and Ovid was performed, searching for the key words: age-related macular degeneration, AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their compound phrases. The search was limited to articles published since 1985 to date. All returned articles were carefully screened and their references were manually reviewed for additional relevant data. The webpage www.clinicaltrials.gov was also accessed in search of relevant research trials. RESULTS: A total of 366 articles were reviewed, including 64 additional articles extracted from the references and 25 webpages and online databases from different institutions. At the end, only 244 references were included in this review. CONCLUSION: Age-related macular degeneration is a complex multifactorial disease that has an uneven manifestation around the world but with one common denominator, it is increasing and spreading. The economic burden that this disease poses in developed nations will increase in the coming years. Effective preventive therapies need to be developed in the near future.

Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease.

Objective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases. Design: Experimental study. Subjects: Brown Norway rats and New Zealand White Cross rabbits. Methods: Preclinical study data of RO-101 in terms of target-specific enzyme-linked immunosorbent assay binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser choroidal neovascular membrane animal model, human umbilical vein endothelial cell migration, and biocompatibility was obtained. Where applicable, study data were compared with other anti-VEGF agents. Main Outcome Measures: Binding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. Results: RO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable to or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. Conclusions: RO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates a strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Current knowledge and trends in age-related macular degeneration: today's and future treatments.

PURPOSE: To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject. METHODS: An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials. RESULTS: A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review. CONCLUSION: Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.

Experimental measure of retinal impact force resulting from intraocular foreign body dropped onto retina through media of differing viscosity.

BACKGROUND: To evaluate and compare the perfluorocarbon liquid, silicone oil, and viscoelastic against standard saline, in their ability to dampen the impact force of a foreign body, dropped within the eye. In an experimental surgical model in where cohesive and adhesive forces of the substances are not enough to float heavy-than-water foreign bodies. METHODS: A model of ophthalmic surgery was constructed. A BB pellet was dropped from 24 mm onto a force transducer through four different fluids: balanced salt solution, perfluoro-n-octane, viscoelastic, and silicone oil. The impact energy (force) for each case was measured and recorded by the force transducer. The mean force of impact for each fluid was compared using the Student t-test. RESULTS: Silicone oil resulted in the lowest force of impact. Both silicone oil and viscoelastic dampened the impact an order of magnitude more than perfluoro-n-octane and balanced salt solution. CONCLUSIONS: Silicone oil and viscoelastic cushioned the force from a dropped BB. They may be useful adjuncts to prevent iatrogenic retinal injury during vitrectomy for intraocular foreign body removal.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Kocuria Endophthalmitis: Clinical Spectrum and Long-term Outcomes.

PURPOSE: To expand the knowledge regarding the clinical presentation of Kocuria endophthalmitis. METHODS: We included six cases of Kocuria endophthalmitis between January 2018 and December 2020. From all cases, we collected general demographic data, relevant medical, ophthalmological history, microbiological and antibiotic sensitivity results. All cases had a minimum follow-up of 9 months. All cases were treated with intravitreal moxifloxacin and dexamethasone and pars plana vitrectomy. Undiluted vitreous, corneal, conjunctival, and aqueous samples were cultured and analyzed with the Vitek 2 system. RESULTS: The prevalence of Kocuria endophthalmitis was 6%. (95%CI: 2.26%-12.73%). The mean age at diagnosis was 60.5 ± 15.5 years. All patients had poor visual acuity, severe pain, and severe conjunctival hyperemia at diagnosis. Only one case had a significant improvement in visual acuity at the end of the follow-up. CONCLUSION: Kocuria spp are an emerging cause of endophthalmitis and should be considered as part of the differential diagnosis.

Risk of Posterior Capsular Rupture during Phacoemulsification in Patients with the History of Anti-VEGF Intravitreal Injections: Results from the Pan-American Collaborative Retina Study (PACORES) Group.

PURPOSE: To assess the risk for capsular rupture during routine phacoemulsification in patients with a history of anti-VEGF injections and other possible risk modifiers such as treatment patterns, type of anti-VEGF agent, and experience of the surgeon, among others. METHODS: This study reviewed the medical records of 11,129 patients from 7 different hospitals in 5 countries. The study included 939 patients that underwent routine phacoemulsification and had a history of anti-VEGF therapy. We excluded patients with known risk factors for capsular rupture, as well as patients with a history of other retinal procedures. The study extracted data regarding general demographics, the number of previous injections, type of anti-VEGF agent, details of cataract surgery, and anti-VEGF treatment patterns. RESULTS: Overall prevalence of posterior capsular rupture: 7.45% (95% CI: 5.9-9.32%). The mean number of injections per patient was 3.37 ± 2.8. More than 50% of the patients received their last anti-VEGF injection within three months before cataract surgery. The complication rate during intravitreal injections was 1.07%. In the univariate analysis, the experience of the cataract surgeon (inexperience surgeons; OR: 2.93) and the history of prior anti-VEGF therapy (OR: 1.77) were significant risk indicators for PCR (p < 0.05). However, after controlling for age in the multivariate analysis, the trend did not reach a statistical significance. CONCLUSION: The risk for capsular rupture is higher in patients with a history of intravitreal anti-VEGF injections.

Comparison of the biometric values obtained by two different A-mode ultrasound devices (Eye Cubed vs. PalmScan): a transversal, descriptive, and comparative study.

BACKGROUND: To assess the reliability of the measurements obtained with the PalmScan, when compared with another standardized A-mode ultrasound device, and assess the consistency and correlation between the two methods. METHODS: Transversal, descriptive, and comparative study. We recorded the axial length (AL), anterior chamber depth (ACD) and lens thickness (LT) obtained with two A-mode ultrasounds (PalmScan A2000 and Eye Cubed) using an immersion technique. We compared the measurements with a two-sample t-test. Agreement between the two devices was assessed with Bland-Altman plots and 95% limits of agreement. RESULTS: 70 eyes of 70 patients were enrolled in this study. The measurements with the Eye Cubed of AL and ACD were shorter than the measurements taken by the PalmScan. The differences were not statistically significant regarding AL (p < 0.4) but significant regarding ACD (p < 0.001). The highest agreement between the two devices was obtained during LT measurement. The PalmScan measurements were shorter, but not statistically significantly (p < 0.2). CONCLUSIONS: The values of AL and LT, obtained with both devices are not identical, but within the limits of agreement. The agreement is not affected by the magnitude of the ocular dimensions (but only between range of 20 mm to 27 mm of AL and 3.5 mm to 5.7 mm of LT). A correction of about 0.5 D could be considered if an intraocular lens is being calculated. However due to the large variability of the results, the authors recommend discretion in using this conversion factor, and to adjust the power of the intraocular lenses based upon the personal experience of the surgeon.

Autologous full-thickness retinal transplant for refractory large macular holes.

BACKGROUND: Despite the constant refinement of techniques and surgical aids, extremely large and refractory macular holes continue to have poor surgical outcomes with the current standard of care. The objective of the present study is to assess the anatomical and functional outcomes, as well as the structural change through time, of the optical coherence tomography of patients with refractory macular holes treated with a full-thickness autologous retinal transplant. METHODS: Prospective, case series. We include patients with a clinical diagnosis of refractory macular holes with a minimum diameter of at least 500 µm. All the patients had a comprehensive ophthalmological examination, which included a best-corrected visual acuity assessment, fundus examination, and optical coherence analysis. All the patients underwent a 23-gauge pars plana vitrectomy with a full-thickness retinal transplant and silicone oil tamponade (5000 cs<). Follow-up was done at 1, 3, 6, and 12 months. Statistical analysis was done with a test for repeated measurements and Bonferroni correction, with an alpha value of 0.05 for statistical significance and a Mann-Whitney U test for nonparametric continuous variables. RESULTS: We enrolled 13 eyes from 13 patients (mean age: 67.15 years) with refractory macular holes, with a mean base diameter of 1615.38 ± 689.19 µm and a minimum diameter of 964.08 ± 709.77 µm. The closure rate after 12 months of follow-up was 76.92%. Six patients with a closed macular hole at the end of the follow-up had complete recovery of the myoid/ellipsoid layer. The remaining showed a 44.9% reduction of the initial gap. Most patients formed a pseudofovea and normalization of the internal retinal layers. Despite a positive trend toward visual recovery (p = 0.034), after the correction of the alpha value, the change lost its statistical significance. During follow-up, one patient developed mild proliferative vitreoretinopathy and epiretinal membrane without anatomical or functional consequences. CONCLUSIONS: An autologous full-thickness retinal transplant may improve the anatomical and structural outcome of patients with refractory macular holes. The full safety profile of this new technique is still unknown. More studies are needed in order to assess functional changes through time.