Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Retrobulbar tube shunt: anterior chamber to back of the eye (A2B) efficacy in glaucomatous eyes with uncontrolled IOP.

PURPOSE: The purpose of this study is to examine the efficacy and safety of a commercial model of the retrobulbar shunt, anterior chamber to back of the eye (A2B), in lowering intraocular pressure (IOP) and medication requirements after the failure of all other IOP-lowering therapies, including trabeculectomy with antimetabolites and tube shunt procedures. METHODS: This is a single-site, prospective, nonrandomized concept study. Patients with prior failed tube shunts, or moderate to severe glaucoma refractory to treatment, were included. All subjects underwent A2B shunt implantation. Each subject's IOP and number of medications were assessed from baseline at each time interval using paired t tests. Primary outcome measures were IOP and glaucoma medication use pre- and postoperatively. Complete success is defined as (1) IOP ≤ 21 mmHg; (2) IOP reduction from baseline of ≥ 20%; (3) no reoperation for glaucoma; (4) no loss of light perception vision; (5) no chronic hypotony defined as IOP ≤ 5 mmHg; and (6) no use of supplemental glaucoma medication. "Qualified success" required satisfaction of the same criteria as "complete success" but with the use of supplemental glaucoma medication at 6 months. RESULTS: Nineteen eyes of 19 patients (mean age 39.5 ± 6.4) were followed for 6 months. The mean IOP (mmHg±SEM) at 6 months dropped from baseline of 35.3 ± 2.3 to 18.5 ± 1.1(- 16.8, - 47%; p < 0.0001). The mean number of glaucoma medications (±SEM) at 30, 90, and 180 days decreased from a baseline of 2.4 ± 0.3 to < 0.3 at each interval (p < 0.0002). The complete and qualified success rates at 6 months were 46.6% (7/15) and 66.6% (11/15), respectively. The mean number of prior incisional glaucoma surgeries was 3.2. The percent of patients that had previously failed sub-Tenon tube shunt surgeries was 79%. CONCLUSIONS: The A2B shunt is an effective rescue therapy in patients that have failed other IOP-lowering procedures. By shunting aqueous humor into the retrobulbar space, IOP and number of glaucoma medications required were substantially reduced for the 6-month postoperative assessment interval. The intrinsic properties of the retrobulbar space may limit the risk of fibrosis, the principal cause of bleb failure.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

Efficacy of a Novel Retrobulbar Extension Shunt to Rescue Eyes with Fibrotic Encapsulated Blebs and Uncontrolled Ocular Hypertension.

PURPOSE: Retrobulbar glaucoma shunts are large-bore fenestrated silicone stents that redirect aqueous humor into the retrobulbar space. They were designed to rescue failed standard tube shunts with fibrotic encapsulation in patients with intractable ocular hypertension. This article evaluates longer-term outcomes of a larger population undergoing retrobulbar aqueous redirection. METHODS: Outcomes of all retrobulbar shunts were placed among this progressive-entry surgical population over an 8-year interval. Implants were produced by New World Medical (NWM) in Rancho Cucamonga, California, and AJL in Bilbao, Spain. Mean and percentage IOP reduction and medications required were evaluated at annual intervals, along with pre-operative and final visual acuity. Significance of change was assessed by two-tailed paired t-test. Failure was designated as any eye requiring placement of another shunt or diode-cyclophotocoagulation. All data are included in this analysis regardless of outcome. RESULTS: Thirty-five retrobulbar shunts were implanted (18M, 17F; mean 54.3 years; mean follow-up 32.5 months). Short-term AJL shunt performance was comparable to that of the 26 NWM shunts, for which there was longer-term follow-up. Three shunts (9%) failed: Two eyes required diode at 6 months, one another standard shunt after > 2 years. Preoperative medications averaged 2.6, reduced to 0.4-0.75 medications at each annual assessment (P < 0.0001). IOP was substantially reduced (by 53-57% from mean baseline 29.9-32.5 mmHg to 16.4-18.4 mmHg; P < 0.0008) at every annual follow-up. Visual acuity remained stable (baseline mean VA 0.27, final VA 0.30; P = 0.68). CONCLUSION: Retrobulbar extension shunts can convert tube shunt failures, with high success rate, to eyes with IOP control comparable to successful primary filtration surgery.

Chronology for the Cueva Victoria fossil site (SE Spain): Evidence for Early Pleistocene Afro-Iberian dispersals.

Cueva Victoria has provided remains of more than 90 species of fossil vertebrates, including a hominin phalanx, and the only specimens of the African cercopithecid Theropithecus oswaldi in Europe. To constrain the age of the vertebrate remains we used paleomagnetism, vertebrate biostratigraphy and (230)Th/U dating. Normal polarity was identified in the non-fossiliferous lowest and highest stratigraphic units (red clay and capping flowstones) while reverse polarity was found in the intermediate stratigraphic unit (fossiliferous breccia). A lower polarity change occurred during the deposition of the decalcification clay, when the cave was closed and karstification was active. A second polarity change occurred during the capping flowstone formation, when the upper galleries were filled with breccia. The mammal association indicates a post-Jaramillo age, which allows us to correlate this upper reversal with the Brunhes-Matuyama boundary (0.78 Ma). Consequently, the lower reversal (N-R) is interpreted as the end of the Jaramillo magnetochron (0.99 Ma). These ages bracket the age of the fossiliferous breccia between 0.99 and 0.78 Ma, suggesting that the capping flowstone was formed during the wet Marine Isotopic Stage 19, which includes the Brunhes-Matuyama boundary. Fossil remains of Theropithecus have been only found in situ ∼1 m below the B/M boundary, which allows us to place the arrival of Theropithecus to Cueva Victoria at ∼0.9-0.85 Ma. The fauna of Cueva Victoria lived during a period of important climatic change, known as the Early-Middle Pleistocene Climatic Transition. The occurrence of the oldest European Acheulean tools at the contemporaneous nearby site of Cueva Negra suggest an African dispersal into SE Iberia through the Strait of Gibraltar during MIS 22, when sea-level was ∼100 m below its present position, allowing the passage into Europe of, at least, Theropithecus and Homo bearing Acheulean technology.

New fossil teeth of Theropithecus oswaldi (Cercopithecoidea) from the Early Pleistocene at Cueva Victoria (SE Spain).

The presence of Theropithecus oswaldi in Europe was first reported in 1995 from the Early Pleistocene site of Cueva Victoria (SE Spain), showing the dispersal of this genus above 30° north latitude and into Europe. Later claims of the presence in Italy of Theropithecus in the Early Pleistocene, based on vertebral remains, are controversial. Here we report four additional teeth of T. oswaldi from Cueva Victoria. These and the previously described tooth correspond to a minimum of two individuals. The presence of T. oswaldi in North Africa and SE Iberia during the Early Pleistocene suggests a possible faunal dispersal from Africa into Europe through the Straits of Gibraltar, which would have acted as a filter bridge.

Idiopathic intracranial hypertension in two twin sisters.

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by an increase in the intracranial pressure. Familial cases of IIH are rare and not well-understood. We present two monozygotic twins who developed IIH two years apart. The case involves two monozygotic female twins developing IIH in their 50s. They presented with a history of blurry vision and headaches. The diagnosis included the neurological, radiological and ophthalmological examination, excluding other causes. Both patients received treatment with acetazolamide, successfully resolving the papilloedema and restoring a normal visual field. This case highlights the occurrence of IIH among twins presenting at similar periods, emphasising the potential genetic influence. Clinicians should alert and educate the family regarding the risk factors and potential symptoms of this condition in the unlikely occurrence that other family members are affected.

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

OBJECTIVES: To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. METHODS: Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. RESULTS: A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. CONCLUSION: Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Vitreous substitutes and tamponades - A review of types, applications, and future directions.

Vitreous substitutes and tamponades occupy the vitreous cavity following vitrectomy in the management of various conditions such as retinal detachment, macular hole, and diabetic retinopathy. Such replacements can be for the short term (gases such as sulfur hexafluoride (SF6) and perfluoropropane (C3F8) or long term (such as silicone oils). Certain substitutes such as perfluorocarbon liquids are used only transiently during surgery as "a third hand" or rarely till a few days post surgery. Hydrogels and hyaluronan derivatives are among the newer vitreous substitutes that are showing promise for the future, albeit still under investigation. still being investigated for use as vitreous substitutes. These materials have properties similar to the natural vitreous and may offer advantages such as improved biocompatibility and biodegradability. Although vitreous substitutes are valuable tools in treating vitreoretinal conditions, they carry risks and potential complications such as cataract formation, glaucoma, and inflammation. The current communication extensively reviews the available literature on vitreous tamponades. It details the composition and properties of various vitreous substitutes and tamponades available for the clinician, highlighting the techniques of usage, indications, and limitations.

Traumatic retinal detachment: A contemporary update.

Retinal detachment following ocular trauma (TrRD) is one of the leading causes of blindness and visual impairment worldwide. In the absence of a standardized definition, the diagnosis of traumatic retinal detachment relies on identifying a history of trauma that precedes the detachment. There is an increasing pool of data regarding the etiology and epidemiology of TrRD.Various causes of TrRD mentioned in the literature include work-related eye trauma in construction and manufacturing industries, sports injuries, explosive eye injuries, road traffic accidents, and intraocular foreign bodies. Although there is extensive literature on post-trauma retinal detachments, a comprehensive discussion of its pathogenesis, management, outcomes, and complications is lacking. We offer an in-depth review of the epidemiology, risk factors, pathogenesis, diagnosis, management, and outcomes of TrRD based on the current literature.

Dementia and cataract surgery in Australia and New Zealand.

BACKGROUND: Cataract surgery improves quality of life and reduces cognitive deterioration. OBJECTIVES: This paper discusses the health implications of low vision, commonly related to cataracts, in older adults. A recent publication reported that cataract surgery reduces the risk of dementia by 30% over 10 years. METHODS: We searched Medline from inception to January 2023. We also conducted backward and forward citation searches of included studies and set up alerts to identify studies published after the search date. We performed discussion groups with multidisciplinary experts. RESULTS: This article provides a broad description of the importance of vision for cognitive function. We discuss access to public-funded cataract surgery in Australia and New Zealand and how this impacts population benefits. CONCLUSIONS: We have evidence that cataract surgery can decrease the risk of dementia. This is an important topic that deserves recognition as part of an overall ageing response by policymakers and health professionals.

Gene expression signatures in conjunctival fornix aspirates of patients with dry eye disease associated with Meibomian gland dysfunction. A proof-of-concept study.

BACKGROUND: Meibomian gland dysfunction (MGD) is one of the most common conditions in ophthalmic practice and the most frequent cause of evaporative dry eye disease (DED). However, the immune mechanisms leading to this pathology are not fully understood and the diagnostic tests available are limited. Here, we used the nCounter technology to analyze immune gene expression in DED-MGD that can be used for developing diagnostic signatures for DED. METHODS: Conjunctival cell samples were obtained by aspiration from patients with DED-MGD (n = 27) and asymptomatic controls (n = 22). RNA was purified, converted to cDNA, preamplified and analyzed using the Gene Expression Human Immune V2 panel (NanoString), which includes 579 target and 15 housekeeping genes. A machine learning (ML) algorithm was applied to design a signature associated with DED-MGD. RESULTS: Forty-five immune genes were found upregulated in DED-MGD vs. controls, involved in eight signaling pathways, IFN I/II, MHC class I/II, immunometabolism, B cell receptor, T Cell receptor, and T helper-17 (Th-17) differentiation. Additionally, statistically significant correlations were found between 31 genes and clinical characteristics of the disease such as lid margin or tear osmolarity (Pearson's r < 0.05). ML analysis using a recursive feature elimination (RFE) algorithm selected a 4-gene mRNA signature that discriminated DED-MGD from control samples with an area under the ROC curve (AUC ROC) of 0.86 and an accuracy of 77.5%. CONCLUSIONS: Multiplexed mRNA analysis of conjunctival cells can be used to analyze immune gene expression patterns in patients with DED-MGD and to generate diagnostic signatures.

Dry eye disease in astronauts: a narrative review.

Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut performance, which is why there is a need for further research into the pathophysiology and countermeasures. As an in-flight countermeasure, neurostimulation seems to be among the most promising options.

Retinotomies and retinectomies: A review of indications, techniques, results, and complications.

Retinotomy refers to "cutting" or "incising" the retina, whereas retinectomy denotes "excising" the retina. Retinotomies and retinectomies aid in tackling traction and retinal shortening that persist following membrane dissection and scleral buckling. We performed a literature search using Google Scholar and PubMed, followed by a review of the references procured. All relevant literature was studied in detail and summarized. We discuss the indications of retinotomies and retinectomies for relaxing retinal stiffness, accessing the subretinal space for choroidal neovascular membrane, hemorrhage and abscess clearance, drainage retinotomies to allow retinal flattening, radial retinotomies to release circumferential traction, harvesting free retinal grafts, and prophylactic chorioretinectomies in trauma.

Prospective evaluation of intense pulsed light treatment for meibomian gland dysfunction and blepharitis due to ocular rosacea

Background: Ocular rosacea is a common skin condition leading to dry eye that is difficult to manage. Objectives: To estimate the efficacy and safety of a new intense pulsed light device, Thermaeye Plus, for meibomian gland dysfunction and blepharitis due to ocular rosacea. Materials & Methods: This prospective, longitudinal study included 74 eyes of 37 consecutive patients with ocular rosacea, with mean age of 45.6±11.7 years. Four consecutive sessions were undertaken, including14 flashes with 10 J/cm² on the periocular area and facial cheeks on Day 1, 14, 28, and 49. Clinical evaluation was based on: ocular surface disease index (OSDI) and symptom score questionnaires, quality of live and facial severity degree, non-invasive tear meniscus height, non-invasive tear break up time, corneal fluorescein staining and eyelid margin and meibomian gland assessment. Adverse effects on the eye and periocular area, and systemic complications were evaluated. Results: The OSDI questionnaire showed a decrease in symptoms, achieving normal values in 91.9% of patients. The symptom score showed amelioration, with the most significant changes relating to dryness, foreign body sensation, light sensitivity, and pain. Longitudinal analysis showed the most significant improvement between baseline at Day 1 and 49. All eyelid signs improved, most significantly for telangiectasia/vascularity and blepharitis, leading to a 78% clearance of facial rosacea and 81.1% reduction of flushing. In total, 100% of the patients reported an improvement in their quality of life after treatment and 94.6% a very significant improvement (p<0.001). Conclusion: These results demonstrate that Thermaeye Plus is an effective and safe treatment for ocular rosacea.

Twentieth-Century Paleoproteomics: Lessons from Venta Micena Fossils.

Proteomics methods can identify amino acid sequences in fossil proteins, thus making it possible to determine the ascription or proximity of a fossil to other species. Before mass spectrometry was used to study fossil proteins, earlier studies used antibodies to recognize their sequences. Lowenstein and colleagues, at the University of San Francisco, pioneered the identification of fossil proteins with immunological methods. His group, together with Olivares's group at the University of Granada, studied the immunological reactions of proteins from the controversial Orce skull fragment (VM-0), a 1.3-million-year-old fossil found at the Venta Micena site in Orce (Granada province, southern Spain) and initially assigned to a hominin. However, discrepancies regarding the morphological features of the internal face of the fossil raised doubts about this ascription. In this article, we review the immunological analysis of the proteins extracted from VM-0 and other Venta Micena fossils assigned to hominins and to other mammals, and explain how these methods helped to determine the species specificity of these fossils and resolve paleontological controversies.

Correction: Torres et al. Twentieth-Century Paleoproteomics: Lessons from Venta Micena Fossils. Biology 2022, 11, 1184.

There was an error in the original publication [...].

Current Treatments and Innovations in Diabetic Retinopathy and Diabetic Macular Edema.

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Multiple treatment options have been used over time to attempt to modify the natural progression of the disease in both proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). These two retinal complications are the result of microvascular occlusions and vascular hyperpermeability and are considered one of the leading causes of irreversible blindness in patients of working age. It is now well demonstrated that PDR and DME are associated with increased levels of inflammatory and pro-angiogenic factors in the ocular compartment. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated efficacy in their treatment in large randomized controlled trials and in real-life observational studies. This manuscript aims to provide a comprehensive review of current treatments, including the main drugs used in diabetic pathologic manifestations, as well as new therapeutic alternatives, such as extended-release intraocular devices.

Prospective evaluation of a new intense pulsed light, thermaeye plus, in the treatment of dry eye disease due to meibomian gland dysfunction.

PURPOSE: This study aims to estimate the efficacy and safety of a new intense pulsed light (IPL) Thermaeye Plus for dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). PATIENTS AND METHODS: This is a prospective, longitudinal study of patients with moderate to severe MGD. Treatment consisted of 4 consecutive IPL sessions, 12 flashes with the same energy 8J/cm2 on the periocular area at days 1, 14, 28, and 49. All patients were evaluated before each IPL sessions and 1 and 4 months after the last session. Measuring: Symptoms score and OSDI questionnaire, Non-invasive tear meniscus height (NITMH), Non-invasive break up (NITBUT), Tear osmolarity (TO), Corneal fluorescein staining (CFS) and Eyelid margin and Meibomian gland assessment. The adverse effects on the eye, periocular area, and systemic complications were evaluated. All types of skin pigmentation (Fitzpatrick scale I to VI) were included. RESULTS: The study included 44 consecutive patients (88 eyes), 40 males and 48 females, with a mean age of 52.5±13.6 years, ranging from 22 to 78 years. Significant improvements were observed in single and total signs and symptoms. The most significant changes were observed in dryness, foreign body sensation (p<0.001), and pain (p<0.005). The OSDI questionnaire showed a significant decrease in total symptoms (p<0.003). The percentage of patients with a normal index <13, improved from 23.8% (10 patients) at baseline to 80.9% (34 patients) at last visit, after 23 weeks. Clinical sings also improved, more than 90%, stand out telangiectasia and blepharitis (p<0.002, and p<0.0005, respectively). No statistical differences between age (<40y, 40-60y, and >60y) and gender were observed. The clinical improvement began after the second and third week after the first IPL session, until the end of the IPL treatment (D49). After that, the results maintained stable until the last visit, after 11 weeks. No complications were reported locally, nor in the periocular area as well as systemically. CONCLUSION: Thermaeye Plus, a new IPL for ophthalmic use, is a safe and effective treatment in patients with DED due to MGD, showing improvement from the second week of treatment and maintaining until the last visit, 4 months after the last IPL session (23 weeks of total follow-up). Patients with pigmented skin (Fitzpatrick V or VI) have been treated with no side effects. It is relevant, especially to apply in brown-dark skin populations since complications with other IPL devices have been reported.