The Effect of Phacoemulsification on the Intraocular Pressure of Patients with Open-angle Glaucoma: A Systematic Review and Meta-Analysis.

PRECIS: There is evidence that cataract surgery can reduce intraocular pressure in patients with primary open angle-, normal tension-, or exfoliative glaucoma. The complete effect of phacoemulsification is masked by topical intraocular pressure-lowering medications. PURPOSE: To assess the impact of phacoemulsification and intraocular lens implantation on intraocular pressure (IOP) level in individuals with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), exfoliation syndrome (XFS), normal tension glaucoma (NTG), ocular hypertension (OH) or healthy controls 12 months after the surgery. METHODS: In July 2023, a comprehensive literature review was conducted across six databases. The analysis focused on the phacoemulsification arms of randomized controlled trials (RCTs). The primary outcome of interest was the mean IOP change observed 12 months after phacoemulsification. RESULTS: This meta-analysis included nine arms from nine RCTs, comprising a total of 502 participants. Overall, the average IOP was reduced by 3.77 mmHg (95%CI: -5.55 to -1.99, I2=67.9%) 12 months after surgery. The subgroup analysis, focused on whether a washout period was employed before measuring IOP, revealed that studies with a washout period exhibited a more pronounced IOP reduction of 5.25 mmHg (95%CI: -7.35 to -3.15, I2=0%), while studies without a washout period exhibited a reduction of 3.13 mmHg (95%CI: -5.46 to -0.81, I2=75.8%). The sensitivity analysis for the latter group, excluding an outlier study, showed a reduction of 1.81 mmHg (95%CI: -2.95 to -0.67, I2=0%). CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that cataract surgery meaningfully lowers IOP in POAG, XFG/XFS, or OH 12 months after surgery. However, the use of topical medications masks the precise impact of phacoemulsification upon postoperative IOP. Further research using appropriate washout periods is warranted.

Acute Corneal Melting Induced by the Concomitant Use of a Non-steroidal Anti-inflammatory Agent with an Antiseptic Eye Drop.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed perioperatively to reduce intraoperative prostaglandin release, diminishing pain, preventing miosis, modulating postoperative inflammation, and reducing the incidence of cystoid macular edema (CME). CASE REPORT: A 70-year-old female patient without previous history of ocular or systemic disease was urgently referred to our hospital because of a sudden corneal perforation concerning her left eye (OS). The patient had instilled bromfenac eye drops and antiseptic eye drops twice and four times daily, respectively, for 2 days only, in preparation of scheduled cataract surgery. Slit-lamp examination revealed diffuse inferior corneal melting with a 1 × 2 mm area of full-thickness perforation and a very shallow anterior chamber. Both topical agents were immediately discontinued. Cyanoacrylate glue was applied to seal the perforation and a bandage contact lens was applied together with a topical antibiotic given hourly. Two hours later, the anterior chamber started to reform. The following day, the anterior chamber was fully reformed with a negative Seidel test. At her next follow-up appointment, 1 month later, the glue was detached and the cornea was seen to have successfully healed with only some corneal thinning remaining inferiorly. CONCLUSIONS: Perioperative use of topical NSAIDs in combination with antiseptic eye drops may rarely elicit corneal perforation in certain susceptible elderly individuals. Their use should therefore be carefully monitored.

Evaluation of a Novel Αb Εxterno MicroShunt for the Treatment of Glaucoma.

The surgical management of glaucoma has been revolutionized by the introduction of minimally invasive glaucoma surgery (MIGS). The various MIGS options aim to meaningfully lower intraocular pressure with a better safety profile than traditional glaucoma surgery. The key clinical attributes and the emerging potential of an ab externo MicroShunt (PreserFlo™) are reviewed in the context of published evidence and clinical experience. This novel MicroShunt consists of an 8.5-mm-long tube that is implanted in the eye via an ab externo approach enabling aqueous humor drainage into the sub-Tenon's space through the formation of a bleb, similar in appearance to that created by trabeculectomy. The efficacy and safety of this procedure, the concomitant use of antimetabolites, the impact of tube positioning, and its future value in clinical practice are critically reviewed. Recent evidence has demonstrated the MicroShunt to be less effective than traditional filtration surgery, but with a significant improvement in safety. Cumulative data suggest that the new implant provides tangible clinical benefits to selected patients with glaucoma in need of further intraocular pressure (IOP) lowering. Future research should delineate the precise role of this and other MIGS options in the rapidly evolving glaucoma treatment algorithm.

Emerging Treatment Modalities for Neovascular Age-Related Macular Degeneration: A Systematic Overview.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of irreversible visual loss affecting the quality of life of millions of elderly patients worldwide. Although the introduction of intravitreal injections with anti-vascular endothelial growth factors (anti-VEGF) agents has revolutionized the management of nAMD, their effectiveness and ultimate success are limited by several therapeutic challenges. Consequently, real-world efficacy appears significantly inferior to that reported by randomized controlled trials. Therefore, further innovative, long-term treatment options are essential to improve the prognosis and outcome of nAMD therapy. METHODS: Emerging pharmacological therapies for nAMD and those currently in clinical trials are reviewed and their mechanism of action, safety, and efficacy are discussed. The evidence presented herein has been collected from online databases PubMed, Cochrane library, and the ClinicalTrials.gov site. RESULTS: A number of promising technologies and novel anti-VEGF therapies are currently being tested and some have already reached phase III trials. Anti-VEGF agents with enhanced durability and possibly efficacy, gene therapy, angiogenic targets, alternative drug delivery routes such as sustained delivery implants, drug carriers, and encapsulated cell technology are currently being explored. We briefly discuss the potential value of these options. CONCLUSION: Several options may optimize future nAMD management. On the basis of current, albeit limited evidence, the most promising technology to reach clinical practice soon appears to be the sustained drug delivery options, which may improve visual outcome and reduce the socioeconomic burden of nAMD.

A new look at the safety and tolerability of prostaglandin analogue eyedrops in glaucoma and ocular hypertension.

INTRODUCTION: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. AREAS COVERED: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. EXPERT OPINION: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

Plasma levels of sirtuin and adiponectin in patients with primary open-angle glaucoma, exfoliative glaucoma, and healthy controls.

PURPOSE: To compare plasma levels of sirtuin 1 (SIRT1) and adiponectin (APN) in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), and healthy control subjects. METHODS: This prospective case-control study collected plasma samples from 118 participants. All subjects underwent a comprehensive ophthalmologic examination before the acquisition of a plasma sample. Plasma samples were obtained from 40 POAG, 38 XFG, and 40 healthy control subjects without any evidence of systemic or ocular disease. Serum SIRT1 and APN levels were estimated by an enzyme-linked immunosorbent assay, ELISA (Elabscience, Houston, USA) method. Statistical analysis of results relied on Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square, analysis of variance (ANOVA) tests, and linear regression analysis, where appropriate. RESULTS: A significant decrease in SIRT1 levels was observed in POAG patients compared to healthy controls (p = 0.004, Dunn's test). In contrast, no difference was detected between XFG and POAG patients or healthy controls (p = 0.32 and p = 0.34, respectively, Dunn's test). There was no significant difference in plasma APN levels between the three groups under investigation (p = 0.59, ANOVA). CONCLUSION: Alterations in serum level of SIRT1 may suggest a possible role in POAG via potential effects in neuroprotection and oxidative stress.

A Case-Cohort Study of Exfoliation Risk Factors and Literature Review.

The purpose of the study is to evaluate the risk factors associated with exfoliation in a case-cohort setting and literature review. This single-center, prospective, case-cohort study was carried out from January 2010 to April 2020 on patients operated for cataract surgery by a single surgeon in Lebanon. Forty-nine consecutive patients with exfoliation syndrome (XFS) and 62 consecutive control patients were identified and further investigated for selected systemic (diabetes mellitus, systemic hypertension, asthma, or atopy) and ocular variables (baseline vision, severity of nuclear sclerosis, glaucoma, eye rubbing, history of dry eye, or allergic eye disease). The mean baseline Snellen visual acuity was 20/283 in XFS versus 20/145 in control cases (P = 0.012). XFS also demonstrated significantly denser nuclear sclerosis than controls (P = 0.00958). By univariate analysis, allergic conjunctivitis (15 [30.6%] vs. 2 [3.2%]; P < 0.001), dry eye (20 [40.8%] vs. 13 [21.0%]; P = 0.0133), and habitual rubbing of the eyes (33 [67.3%] vs. 19 [30.6%]; P < 0.001) were associated with the presence of XFS. Habitual ocular rubbing was closely associated with allergic conjunctivitis (odds ratio [OR] = 13.0; 95% confidence interval [CI]: 2.8-58.8; P = 0.032). After multivariable analysis, the following variables showed significant results: glaucoma (OR = 34.5; 95% CI: 4.4-250; P = 0.010), duration of surgery (OR = 5.6; 95% CI 2.43-12.9; P < 0.001), and habitual ocular rubbing (OR = 4.42; 95% CI: 1.97-9.90; P = 0.029). This study shows a novel potential correlation between eye rubbing and XFS in a Lebanese cohort. Chronic eye rubbing induces or may exacerbate preexistent zonular damage in subjects with XFS, hence the need to better manage concurrent ocular surface disorder in these patients.

Glaucoma and neuroinflammation: An overview.

Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching, papillary vessel modifications) consequent to retinal ganglion cell loss, axonal degeneration, and lamina cribrosa remodeling. These modifications tend to be progressive and are the main cause of functional damage in glaucoma. Despite the latest findings about the pathophysiology of the disease, the exact trigger mechanisms and the mechanism of degeneration of retinal ganglion cells and their axons have not been completely elucidated. Neuroinflammation may play a role in both the development and the progression of the disease as a result of its effects on retinal environment and retinal ganglion cells. We summarize the latest findings about neuroinflammation in glaucoma and examine the connection between risk factors, neuroinflammation, and retinal ganglion cell degeneration.

The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability.

Introduction: Preservative-free (PF) medications represent a valuable treatment strategy in the lifelong management of glaucoma. By removing preservative toxicity, PF formulations provide tangible clinical benefits to glaucoma patients worldwide. They improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control.Areas covered: A critical review of the subject is provided, including selected evidence on the safety and tolerability of currently available topical PF formulations. Cumulative evidence confirms that topical PF medications are at least equally efficacious to their preserved equivalents. There is convincing short-term evidence for superior tolerability and safety of PF formulations compared to preserved medications. The long-term benefits and success of PF therapy requires further elucidation.Expert opinion: Successful stepwise administration of medical therapy for glaucoma remains elusive. There is a greater risk for ocular toxicity and therapy failure with preserved topical glaucoma therapy. Currently available and emerging PF therapy options potentially optimize lifelong stepwise glaucoma therapy and may enhance outcome. To avert complications from preservatives leading to poor adherence, ideally, future antiglaucoma therapy should become 100% PF. There are still key aspects of PF therapy that warrant further investigation.

Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future.

The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications worldwide. The pharmacological properties of DTFC reflect those of its two time-tested constituents, i.e., the carbonic anhydrase inhibitor dorzolamide and the non-selective beta-blocker timolol. In regulatory studies DTFC lowers IOP on average by 9 mmHg (32.7%) at peak and by 7.7 mmHg (27%) at trough. In trials DTFC shows equivalence to unfixed concomitant therapy, but in real-life practice it may prove superior owing to enhanced convenience, elimination of the washout effect from the second drop, improved tolerability, and better adherence. PF DTFC became the first PF FC approved, first in unit-dose pipettes, and more recently in a multidose format. Cumulative evidence has confirmed that PF DTFC is at least equivalent in efficacy to preserved DTFC and provides a tangible clinical benefit to patients with glaucoma suffering from ocular surface disease by improving tolerability and adherence. Finally, we identify areas that warrant further investigation with preserved and PF DTFC.

Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review.

INTRODUCTION: Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to. AREAS COVERED: We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs. EXPERT OPINION: It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.

Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review.

SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread.

Management of Full-Thickness Macular Hole in A Genetically Confirmed Case with Usher Syndrome.

INTRODUCTION: Full-thickness macular hole (FTMH) formation is rarely seen in patients with retinitis pigmentosa (RP) and can have an adverse impact on their residual visual function. The underlying mechanisms are unknown, and clinical experience is limited regarding surgical outcomes. Here, we describe the surgical management of FTMH in a young patient with genetically confirmed Usher syndrome, the most common form of syndromic RP. CASE REPORT: A 28-year-old woman presented with blurred vision in her right eye (RE). She had a history of RP and bilateral hearing impairment since childhood. Fundoscopy and spectral-domain optical coherence tomography revealed a FTMH in the RE along with typical RP features bilaterally. After pars plana vitrectomy (PPV) with internal limiting membrane peel and gas tamponade, the FTMH closed. Six months after PPV the patient underwent cataract surgery in the affected eye, and the visual acuity remained stable compared to baseline. The clinical diagnosis of Usher syndrome was genetically confirmed by whole exome sequencing (WES), which revealed the presence of two pathogenic nucleotide variants in trans (compound heterozygosity) in the gene USH2A. CONCLUSION: We report a rare case of successful closure of a FTMH in a patient with Usher syndrome. Surgical treatment of FTMH can help preserve the central vision in RP patients, whose peripheral vision is severely affected.

Serum Apelin and Asymmetric Dimethylarginine Levels in Patients With Exfoliation Syndrome or Exfoliative Glaucoma.

PRéCIS:: Apelin and asymmetric dimethylarginine (ADMA) concentrations, affecting the nitric oxide pathway, were different in the patient group compared with the control subjects. These 2 molecules may have potential effects in vascular pathologies and their possible role in predisposition to vascular comorbidities in exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). PURPOSE: To evaluate apelin and ADMA levels in serum samples from patients with XFS or XFG compared with healthy control subjects. METHODS: Serum ADMA and apelin concentrations were evaluated from 36 and 32 XFS patients; 27 and 24 XFG patients; and 34 and 30 healthy controls, respectively. Subjects without systemic disease (including diabetes mellitus, hypertension, coronary artery disease, obesity) were included in the study and body mass index was calculated in all participants. An enzyme-linked immunosorbent assay and high-performance liquid chromatography were used to determine serum apelin and ADMA concentrations. Independent sample t test, χ test, analysis of variance test, and Pearson test were used for statistical analysis. RESULTS: Mean serum apelin levels of XFG, XFS, and control group were 1063.3±373.4, 1196.7±433.7, and 1343.3±405.1 ng/mL, respectively. Patients with XFG demonstrated significantly lower level of apelin versus controls (P=0.034). Mean serum ADMA concentration was significantly greater in XFS subjects (2.05±0.98 µmol/L) compared with normal controls (1.57±0.58 µmol/L) (P=0.042). No association was detected between ADMA and apelin concentrations and age, sex, and body mass index for both XFS and XFG groups. CONCLUSIONS: Significant alterations in serum levels of apelin and ADMA may suggest potential effects in vascular pathologies and a possible role in predisposition to vascular comorbidities in XFS/XFG.

Author Correction: Vision-related quality of life and symptom perception change over time in newly-diagnosed primary open angle glaucoma patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nanotechnology for Medical and Surgical Glaucoma Therapy-A Review.

Glaucoma is the second leading cause of blindness worldwide. Even though significant advances have been made in its management, currently available antiglaucoma therapies suffer from considerable drawbacks. Typically, the success and efficacy of glaucoma medications are undermined by their limited bioavailability to target tissues and the inadequate adherence demonstrated by patients with glaucoma. The latter is due to a gradual decrease in tolerability of lifelong topical therapies and the significant burden to patients of prescribed stepwise antiglaucoma regimens with frequent dosing which impact quality of life. On the other hand, glaucoma surgery is restricted by the inability of antifibrotic agents to efficiently control the wound healing process without causing severe collateral damage and long-term complications. Evolution of the treatment paradigm for patients with glaucoma will ideally include prevention of retinal ganglion cell degeneration by the successful delivery of neurotrophic factors, anti-inflammatory drugs, and gene therapies. Nanotechnology-based treatments may surpass the limitations of currently available glaucoma therapies through optimized targeted drug delivery, increased bioavailability, and controlled release. This review addresses the recent advances in glaucoma treatment strategies employing nanotechnology, including medical and surgical management, neuroregeneration, and neuroprotection.

The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

INTRODUCTION: Keratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000-1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL. METHODS: PubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," "proteins", "collagen" and "cornea'' were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL. RESULTS: A total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control. CONCLUSION: The pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

Combined Pupilloplasty and Retropupillary Iris-Claw Intraocular Lens Implantation with DSAEK in a Patient with Traumatic Iridoplegia, Aphakia and Corneal Decompensation.

PURPOSE: To report the management of a patient with traumatic mydriasis, aphakia and corneal decompensation with a triple procedure: simultaneous pupilloplasty and retropupillary iris-claw intraocular lens (IOL) implantation combined with Descemet stripping automated endothelial keratoplasty (DSAEK). RESULTS: An 88-year-old woman was referred to our Institute for consultation on her left eye. The patient had undergone surgical removal of the IOL, without re-implantation, in her left eye 10 months prior to presentation due to traumatic IOL dislocation. At the time of examination, corrected distance visual acuity was counting fingers and intraocular pressure was 10 mmHg. Slit-lamp examination revealed iridoplegia, aphakia and corneal edema. The patient underwent simultaneous pupilloplasty and retropupillary iris-claw IOL implantation combined with DSAEK. Six months postoperatively, the corneal graft was attached and clear, the iris was well reconstructed and almost round, and the iris-claw IOL was in place. CONCLUSIONS: Simultaneous pupilloplasty and retropupillary iris-claw IOL implantation combined with DSAEK was shown to be a safe surgical technique in a patient with traumatic mydriasis, aphakia and corneal decompensation.

Intraoperative Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) During Penetrating Keratoplasty for the Management of Fungal Keratitis in an Immunocompromised Patient.

INTRODUCTION: To present a novel intraoperative application of photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) in the management of post-penetrating keratoplasty (PKP) multiresistant fungal keratitis in a patient with irradiation-related local immunosuppression. CASE REPORT: A 62-year-old female underwent uneventful PKP for the management of post-irradiation actinic keratopathy. Three months postoperatively, she presented with a diffuse corneal melting abscess that was infiltrating the donor-recipient junction. Despite intensive antibiotic and antifungal therapy, corneal melting progressed to graft perforation. A repeat PKP combined with intraoperative PACK-CXL was performed. PACK-CXL was applied initially on the infected graft, involving the corneoscleral rim and then following placement of the donor button. No intra- or postoperative graft-related complications were encountered. No signs of infection were noted, and the graft remained clear during the 9-month follow-up period. CONCLUSION: Intraoperative PACK-CXL combined with PKP appears to be a safe and effective technique for the management of post-PKP resistant fungal keratitis.