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.

Changing from preserved, to preservative-free cyclosporine 0.1% enhanced triple glaucoma therapy: impact on ocular surface disease-a randomized controlled trial.

OBJECTIVE: Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. METHODS: A single-centre, masked, prospective, placebo-controlled, crossover trial of 41 well-controlled open-angle glaucoma subjects with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination (DTFC) therapy was conducted. Subjects were randomized to preservative-free (PF) tafluprost and DTFC with either placebo or cyclosporine 0.1% drops for 6 months and were then crossed over to the opposite therapy. Oxford score of ocular staining was the primary outcome; osmolarity, matrix-metalloproteinase-9 (MMP-9) testing, tear film break-up time (TFBUT), meibomian gland dysfunction (MGD), punctum evaluation, adverse events and diurnal intraocular pressure (IOP) comprised secondary outcomes. RESULTS: GTR-OSD findings improved with PF therapy. At 6 months the triple PF with placebo group showed improvement compared to baseline in mean Oxford score (mean difference [MD]:-3.76; 95% confidence interval [CI]:-4.74 to -2.77; p < 0.001), osmolarity (MD:-21.93; 95%CI:-27.61 to -16.24 mOsm/l; p < 0.001), punctum stenosis (p = 0.008) and conjunctival hyperaemia (p < 0.001). Similar improvements occurred in the cyclosporine enhanced period, which also provided greater improvement in MMP-9 positivity (24 vs 66%; p < 0.001) and TFBUT (p = 0.022). The cyclosporine group was superior vs placebo in mean Oxford score (MD:-0.78; 95%CI:-1.40 to -0.15); p < 0.001), itchiness and objective adverse events (p = 0.034). Cyclosporine elicited more stinging vs placebo (63 vs 24%; p < 0.001). Both PF regimens reduced mean diurnal IOP more than preserved therapy (14.7 vs 15.9 mmHg; p < 0.001). CONCLUSIONS: Changing from preserved to PF glaucoma medications improves ocular surface health and IOP control. Topical cyclosporine 0.1% further reverses GTR-OSD.

Correction to: 24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

In the original article, the incorrect Open Access License type has been incuded.

How Successful is Switching from Bevacizumab or Ranibizumab to Aflibercept in Age-Related Macular Degeneration? A Systematic Overview.

Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina practice and the management and eventual outcome of nAMD. Recent research has focused on evaluating and comparing the efficacy of the two most widely employed anti-VEGF agents, bevacizumab and ranibizumab; however, a subgroup of patients with nAMD demonstrates a suboptimal response to standard therapy. We have therefore conducted a review of pertinent studies published until August 2018 which have documented the clinical efficacy when switching to a different anti-VEGF. Evidence on baseline disease characteristics, injection frequency and disease outcome has been obtained for patients treated with ranibizumab 0.5 mg and/or bevacizumab 1.25 mg and were switched to aflibercept 2 mg. Our review identified 45 studies investigating switching to aflibercept. Our review showed a clear anatomical benefit after the switch in terms of central retinal thickness and pigment epithelium detachment characteristics, whereas the functional outcomes were variable. Remarkable heterogeneity was documented among the relevant studies with regard to several factors including the baseline characteristics of the cohorts, the non-response definition and previous treatment protocols. Larger prospective trials with appropriate control arms are therefore required to elucidate the potential benefit when switching between anti-VEGF agents in refractory nAMD.

Preservative-free tafluprost/timolol fixed combination: comparative 24-h efficacy administered morning or evening in open-angle glaucoma patients.

Background: Ideal dosing for the preservative-free (PF) tafluprost/timolol fixed combination (TTFC) remains to be elucidated. Research design and methods: This study was a prospective, observer-masked, placebo-controlled, crossover, comparison in 42 consecutive open-angle glaucoma patients whose intraocular pressure (IOP) was insufficiently controlled with preserved latanoprost monotherapy (mean 24-h IOP >20 mmHg). Patients were randomized to either morning (08:00) or evening (20:00) PF TTFC for 3 months and then crossed over. After each treatment period, patients underwent habitual 24-h IOP monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Results: Mean 24-h IOP on latanoprost was 22.2±3.9 mmHg. Both PF TTFC dosing regimens obtained greater reduction in mean 24-h, daytime, nighttime, and peak 24-h IOP (P < 0.001). Evening dosing provided tighter 24-h IOP fluctuation versus latanoprost (P < 0.001). Evening dosing was superior to morning dosing at four time points (P < 0.01), for the mean daytime IOP (P < 0.001) and mean 24-h IOP fluctuation (P < 0.001). Hyperemia was more common with preserved latanoprost (21.4 vs. 7.1%; P = 0.031). Patients (n = 19; 45%) preferred evening dosing. Conclusions: PF TTFC provided greater 24-h IOP control and less hyperemia compared with preserved latanoprost. Evening administration of this novel medication offered superior 24-h efficacy. Trial registration: Clinicaltrials.gov (NCT03612817).

A Review of the Clinical Usefulness of Selective Laser Trabeculoplasty in Exfoliative Glaucoma.

In the last decade, selective laser trabeculoplasty (SLT) has been commonly used in the management of several different types of glaucoma, as either primary or adjunct therapy. The technique has an excellent safety profile and is at least as effective as argon laser trabeculoplasty. Although the actual mechanism of action of SLT remains unclear, evidence has shown that it does not induce morphologically evident trabecular meshwork alterations. SLT's non-disruptive mode of action offers the advantage of repeatability. Exfoliation glaucoma (XFG) is a secondary open-angle glaucoma with unfavorable intraocular pressure (IOP) characteristics, which typically carries a poorer long-term prognosis than primary open-angle glaucoma. Consequently, patients with XFG often need multiple medications to achieve IOP levels that prevent disease progression. Because complicated pharmacotherapy regimens undermine the long-term tolerability and compliance of patients with XFG, options such as SLT may decrease the burden of multiple therapies and ultimately improve prognosis. In fact, SLT may be a particularly attractive option in XFG because the pigment-laden trabecular tissue of these patients enhances the absorption of laser energy and thus augments the biologic effects induced by this treatment. The current article reviews the postulated mechanisms of action of SLT, discusses practical aspects of SLT therapy, and examines selected peer-reviewed literature pertaining to the clinical usefulness of this modality in XFG patients.

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

INTRODUCTION: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). METHODS: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. RESULTS: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). CONCLUSIONS: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02802137). FUNDING: Santen.

Twenty-four-hour intraocular pressure monitoring in normotensive patients undergoing chronic hemodialysis.

PURPOSE: To investigate 24-hour intraocular pressure (IOP) changes caused by hemodialysis (HD). METHODS: A prospective, observational, comparative 24-hour trial was performed on consecutive subjects with normal IOP undergoing maintenance HD 3 days a week between 13:00 and 17:00 hours in an academic setting. Following a comprehensive ocular assessment, those with conditions that may influence IOP were excluded and one eye was randomly selected. Twenty-four-hour IOP monitoring was performed on HD day 1 and then on a day without HD. The IOP was measured at 10:00, 13:00, 15:00, 17:00, 22:00, 02:00, and 06:00 employing Goldmann and Perkins tonometry on habitual position. During the course of 1 year, 18 patients completed the study. RESULTS: Monitoring of IOP on HD day showed a significantly higher mean 24-hour IOP (15.4 ± 2.7 vs 14.1 ± 2.2 mm Hg; p = 0.025), higher mean peak 24-hour IOP (18.5 ± 3.5 vs 15.8 ± 2.5 mm Hg; p = 0.003), and wider 24-hour IOP fluctuation (6.2 ± 2.3 vs 4.0 ± 1.9 mm Hg; p = 0.001). When individual time points were compared, IOP was significantly higher at 17:00 on HD day, reflecting a gradual IOP elevation during HD (p = 0.021). Further, during the HD procedure (13:00-17:00), the mean IOP was significantly higher on a HD day (16.4 ± 3.0 vs 14.7 ± 2.4 mm Hg; p = 0.004). CONCLUSIONS: This prospective, before/after trial suggests that HD significantly impacts 24-hour IOP characteristics in normotensive eyes. The long-term significance of these findings requires further elucidation in normotensive patients and, predominantly, in patients with glaucoma undergoing HD.

Critical Appraisal on Orbital Decompression for Thyroid Eye Disease: A Systematic Review and Literature Search.

INTRODUCTION: Orbital decompression is the indicated procedure for addressing exophthalmos and compressive optic neuropathy in thyroid eye disease. There are an abundance of techniques for removal of orbital bone, fat, or a combination published in the scientific literature. The relative efficacy and complications of these interventions in relation to the specific indications remain as yet undocumented. We performed a systematic review of the current published evidence for the effectiveness of orbital decompression, possible complications, and impact on quality of life. METHODS: We searched the current databases for medical literature and controlled trials, oculoplastic textbooks, and conference proceedings to identify relevant data up to February 2015. We included randomized controlled trials (RCTs) comparing two or more interventions for orbital decompression. RESULTS: We identified only two eligible RCTs for inclusion in the review. As a result of the significant variability between studies on decompression, i.e., methodology and outcome measures, we did not perform a meta-analysis. One study suggests that the transantral approach and endonasal technique had similar effects in reducing exophthalmos but the latter is safer. The second study provides evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures. CONCLUSION: Most of the published literature on orbital decompression consists of retrospective, uncontrolled trials. There is evidence from those studies that removal of the medial and lateral wall (balanced) and the deep lateral wall decompression, with or without fat removal, may be the most effective surgical methods with only few complications. There is a clear unmet need for controlled trials evaluating the different techniques for orbital decompression. Ideally, future studies should address the effectiveness, possible complications, quality of life, and cost of each intervention.

24-hour efficacy of travoprost/timolol BAK-free versus latanoprost/timolol fixed combinations in patients insufficiently controlled with latanoprost.

INTRODUCTION: To compare the 24-h intraocular pressure (IOP) control and tolerability of travoprost/timolol benzalkonium chloride (BAK)-free (TTFC) vs. latanoprost/timolol fixed combination preserved with BAK (LTFC) in open-angle glaucoma patients insufficiently controlled with latanoprost 0.005% monotherapy given once in the evening. METHODS: The authors have conducted a prospective, observer-masked, active-controlled, cross-over, comparison study. Qualified open-angle glaucoma patients who demonstrated a latanoprost-treated morning IOP (10:00 ± 1 h) greater than 20 mmHg on two separate visits were randomized for 3 months to receive either TTFC or LTFC. Patients were then crossed over to the opposite treatment for another 3 months. At the end of the latanoprost run-in and after each 3-month therapy period patients underwent 24-h IOP monitoring in the habitual position using Goldmann applanation tonometry in the sitting position during the day (10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the supine position at night (02:00 and 06:00). Selected ocular surface parameters were evaluated after each therapy period. RESULTS: Forty-two open-angle glaucoma patients completed the study. The mean 24-h baseline IOP on latanoprost was 21.5 ± 1.6 mmHg. Both fixed combinations significantly reduced the IOP at each time point, for the mean, peak and fluctuation of 24-h IOP compared with latanoprost monotherapy (P < 0.01). When the two fixed combinations were compared directly, TTFC provided significantly lower mean 24-h IOP (18.9 ± 2.2 mmHg) vs. LTFC (19.3 ± 2.3 mmHg) (P = 0.004) and significantly lower IOP at 18:00 (18.6 ± 2.5 vs. 19.5 ± 2.7 mmHg for LTFC) (P < 0.001). Further, TTFC demonstrated significantly better tear film break-up time (5.15 vs. 4.65 s), corneal stain (1.5 vs. 1.8) and Schirmer I test (9.9 vs. 9.2 mm) compared with LTFC after 3 months of therapy (P < 0.01 for all comparisons). CONCLUSION: The mean 24-h IOP lowering of TTFC was statistically more significant compared to LTFC in patients insufficiently controlled with latanoprost monotherapy. Measurement of ocular surface health and tear film status favored the BAK-free TTFC compared to LTFC.

New perspectives on lamellar keratoplasty.

Lamellar (anterior and posterior) keratoplasty entails the surgical replacement of diseased-only corneal tissue, while healthy host corneal tissue is preserved. Selective keratoplasty offers several advantages in comparison to penetrating keratoplasty such as a lower rate of graft rejection, less endothelial cell loss, faster/superior visual rehabilitation and enhanced resistance to closed injury. The surgical approach of "partial corneal transplantation" may be divided into anterior and posterior: techniques including superficial and deep anterior lamellar keratoplasty (SALK and DALK, respectively) and endothelial keratoplasty as well as Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). These novel surgical procedures are rapidly becoming the preferred therapy option for specific corneal dysfunctions involving the corneal stroma (SALK, DALK), or corneal endothelium (DSAEK, DMEK). During the past decade, the continuing advancement of surgical techniques and the development of innovative surgical instruments have significantly enhanced corneal transplantation. Lamellar keratoplasty techniques facilitate corneal surgery, provide patients with superior outcomes and can successfully restore vision in corneal-related blindness. Nevertheless, more long-term evidence is needed to better evaluate these promising new techniques.

An overview of corneal collagen cross-linking (CXL).

Corneal collagen cross-linking (CXL) was first described over a decade ago and is now considered to be one of the most important surgical innovations of modern ophthalmology. Prior to its introduction, no interventions were available to arrest, or slow down ectatic disease progression, with corneal transplantation required in the majority of cases. Unlike earlier treatments of corneal ectasias that attempted to only improve the consequences of the disease, CXL aims to address the corneal biomechanical weakening itself. The long-term safety and efficacy of CXL have been established in several studies that have documented significant improvements in all outcome measures (visual acuity, spherical equivalent, astigmatism, and keratometric findings). The emerging combination of CXL with other interventions (termed 'CXL plus') optimizes the visual and topographic outcomes. This, along with the expansion of the techniques' indications for other clinical conditions, such as microbial keratitis, highlights the continuous improvement of the initial technique and confirms its wide acceptance. Overall, CXL has already demonstrated much promise and has several clinical indications, representing a clear example of recent advances in ocular therapy.

Latanoprost/timolol fixed combination for the treatment of glaucoma.

INTRODUCTION: Glaucoma is a multifactorial optic neuropathy that can lead to progressive and irreversible loss of vision. Today there are > 60 million glaucoma patients worldwide, and this figure is rising due to aging. The aim of glaucoma therapy is to maintain the patient's visual function and quality of life by means of intraocular pressure (IOP) reduction, which currently constitutes the only evidence-based approach. AREAS COVERED: Briefly discussed are selected, recent evidence on antiglaucoma fixed combinations. Then the efficacy and safety of the latanoprost/timolol fixed combination is comprehensively reviewed. EXPERT OPINION: The latanoprost/timolol fixed combination can be a helpful stepwise therapeutic option in patients whose IOP is insufficiently controlled with monotherapy options. Future research is needed to better delineate the role and value of this medication in glaucoma therapy.

Twenty-four hour efficacy with preservative free tafluprost compared with latanoprost in patients with primary open angle glaucoma or ocular hypertension.

AIM: To compare 24 h intraocular pressure (IOP) control obtained with preservative free (PF) tafluprost 0.0015% versus branded preservative containing latanoprost 0.005% administered as first choice monotherapy in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: This prospective, observer-masked, crossover study included consecutive newly diagnosed patients with POAG or OHT, and baseline IOP between 24 and 33 mm Hg. Qualifying patients underwent baseline untreated 24 h IOP monitoring in habitual positions, with Goldmann tonometry at times 10:00, 14:00, 18:00 and 22:00, and Perkins supine tonometry at times 02:00 and 06:00. They were then randomised to either latanoprost or tafluprost, administered in the evening, for 3 months and then switched to the opposite therapy for another 3 months. 24 h monitoring was repeated at the end of each treatment period. RESULTS: 38 patients completed the study. Mean untreated 24 h IOP (24.9 mm Hg) was significantly reduced with both prostaglandins (p<0.001). Tafluprost demonstrated similar mean 24 h efficacy compared with latanoprost (17.8 vs 17.7 mm Hg; p=0.417). Latanoprost demonstrated significantly better 24 h trough IOP (15.9 vs 16.3 mm Hg; p=0.041) whereas tafluprost provided significantly lower 24 h IOP fluctuation (3.2 vs 3.8 mm Hg; p=0.008). No significant difference existed between the two prostaglandins for any adverse event. CONCLUSIONS: PF tafluprost achieved similar 24 h IOP reduction to branded latanoprost. The current study highlights the importance of complete assessment of efficacy over 24 h. CLINICAL TRIALS REGISTRATION: NCT01162603.

Comparison of 24-hour intraocular pressure reduction obtained with brinzolamide/timolol or brimonidine/timolol fixed-combination adjunctive to travoprost therapy.

BACKGROUND: To determine the adjunctive 24-h efficacy obtained with brinzolamide/timolol, or brimonidine/timolol fixed combinations (FCs) in open-angle glaucoma patients insufficiently controlled on travoprost monotherapy. METHODS: Prospective, observer-masked, active controlled, crossover, comparison. Qualified primary open-angle or exfoliative glaucoma patients with a baseline intraocular pressure (IOP) >18 mm Hg at 10:00 on travoprost monotherapy were randomized for 3 months to either brinzolamide/timolol, or brimonidine/timolol FC therapy adjunct to travoprost. Patients were then crossed-over to the opposite therapy for another 3 months. At baseline and at the end of each treatment period, the patients underwent 24-h IOP monitoring. RESULTS: Fifty patients completed the study. The mean 24-h baseline IOP on travoprost monotherapy was 20.1 mm Hg [95% confidence interval (CI): 19.6, 20.7 mm Hg]. Both adjunctive FC therapies significantly reduced the IOP at each time point and for the mean 24-h IOP (P<0.001) compared with travoprost monotherapy. Brinzolamide/timolol FC provided a significantly lower mean 24-h IOP (17.2 mm Hg, 95% CI: 16.4, 17.9 mm Hg) than brimonidine/timolol FC (18.0 mm Hg, 95% CI: 17.3, 18.8 mm Hg) (P<0.001). For all the 3 timepoints between 18:00 and 02:00, the brinzolamide/timolol FC provided a significantly lower IOP than the brimonidine/timolol FC (P≤0.036). For the other 3 timepoints, no significant differences were detected. CONCLUSIONS: This study demonstrated that both FCs provide statistically and clinically significant incremental 24-h IOP lowering to travoprost monotherapy. The brinzolamide/timolol FC however achieves a better mean 24-h IOP control owing to the greater efficacy in late afternoon and during the night.