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Eleftherios Chatzimichail,1 Kristina Pfau,1,2 Zisis Gatzioufas,1 Georgios D Panos3,4 1Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland; 2Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; 3Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 4Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UKCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: Ranibizumab, is a humanized, monoclonal antibody fragment that binds and inactivates vascular endothelial growth factor-A (VEGF-A) and VEGF-B. One of the main indications for an intravitreal treatment with ranibizumab is age-related macular degeneration (AMD), which is a retinal disease with a high worldwide socioeconomic impact. Biosimilars constitute biological products that demonstrate similar pharmacodynamic and pharmacokinetic characteristics with a reference product, as well as comparable clinical efficacy, safety and immunogenicity. Since the approval of the first biosimilar Razumab, there has been a variety of new biosimilars available on the market. They offer the advantage of the same good clinical and safety results at a better price. All Ranibizumab biosimilars that have gained approval were tested in double masked Phase 3 clinical studies. The use of Ranibizumab biosimilars in neovascular AMD is well reported in the bibliography. Nevertheless, over the last few years, there is a tendency of using biosimilars in other retinal diseases like retinopathy of prematurity (ROP), diabetic macular edema (DME) or polypoidal choroidal vasculopathy (PCV). In conclusion, ranibizumab biosimilars offer a promising avenue for the management of retinal diseases, especially in countries with lower socioeconomic status, where there is lack of availability of innovator ranibizumab. However, further research is required to fully explore their efficacy, safety, and long-term outcomes in a plethora of retinal diseases.Keywords: ranibizumab, biosimilars, age-related macular degeneration, diabetic macular edema, retinal disorders, retinal vein occlusion, cost-effectiveness

Stefan Futterknecht,1,2 Eleftherios Chatzimichail,1 Konstantin Gugleta,1,3 Georgios D Panos,4,5,* Zisis Gatzioufas1,3,* 1Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland; 2Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; 3Department of Ophthalmology, School of Medicine, University of Basel, Basel, Switzerland; 4Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 5Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK*These authors contributed equally to this workCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: The cornea, as the outermost layer of the eye, plays a crucial role in vision by focusing light onto the retina. Various diseases and injuries can compromise its clarity, leading to impaired vision. This review aims to provide a thorough overview of the pharmacological properties, therapeutic potential and associated risks of Rho-associated protein kinase (ROCK) inhibitors in the management of corneal diseases. The article focuses on four key ROCK inhibitors: Y-27632, fasudil, ripasudil, and netarsudil, providing a comparative examination. Studies supporting the use of ROCK inhibitors highlight their efficacy across diverse corneal conditions. In Fuchs’ endothelial corneal dystrophy, studies on the application of Y-27632, ripasudil, and netarsudil demonstrated noteworthy enhancements in corneal clarity, endothelial cell density, and visual acuity. In pseudophakic bullous keratopathy, the injection of Y-27632 together with cultured corneal endothelial cells into the anterior chamber lead to enhanced corneal endothelial cell density and improved visual acuity. Animal models simulating chemical injury to the cornea showed a reduction of neovascularization and epithelial defects after application of fasudil and in a case of iridocorneal endothelial syndrome netarsudil improved corneal edema. Addressing safety considerations, netarsudil and ripasudil, both clinically approved, exhibit adverse events such as conjunctival hyperemia, conjunctival hemorrhage, cornea verticillata, conjunctivitis, and blepharitis. Monitoring patients during treatment becomes crucial to balancing the potential therapeutic benefits with these associated risks. In conclusion, ROCK inhibitors, particularly netarsudil and ripasudil, offer promise in managing corneal diseases. The comparative analysis of their pharmacological properties and studies supporting their efficacy underscore their potential therapeutic significance. However, ongoing research is paramount to comprehensively understand their safety profiles and long-term outcomes in diverse corneal conditions, guiding their optimal application in clinical practice.Keywords: rho kinase inhibitors, cornea, corneal diseases, corneal dystrophies, Fuchs’ endothelial corneal dystrophy, corneal transplantation

Yusuf Mushtaq,1,* Maryam M Mushtaq,2,* Zisis Gatzioufas,3 Matteo Ripa,4 Lorenzo Motta,5 Georgios D Panos1 1Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust & School of Medicine, University of Nottingham, Nottingham, UK; 2Department of Acute Medicine, Luton and Dunstable University Hospitals NHS Trust, Luton, UK; 3Department of Ophthalmology, Basel University Hospital & University of Basel School of Medicine, Basel, Switzerland; 4Ophthalmology Unit, “Fondazione Policlinico Universitario A. Gemelli IRCCS”, Rome, Italy; 5Department of Ophthalmology, William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Kent, UK*These authors contributed equally to this workCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.com Lorenzo Motta, Department of Ophthalmology, William Harvey Hospital, Kennington Road, Willesborough, Ashford, Kent, TN24 0LZ, UK, Tel +44 1233 633331, Email lorenzo.motta@nhs.netAbstract: Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non–infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.Keywords: Iluvien, steroid implant, diabetic macular oedema, intravitreal implant, posterior uveitis, retinal vein occlusion

Mohamed Elalfy,1– 3,* Sundas Maqsood,1,* Shady Soliman,3 Sherif Momtaz Hegazy,3 Ahmed Abdou Hannoun,3 Zisis Gatzioufas,1,4 Damian Lake,1 Samer Hamada1 1Corneo Plastic Unit, Queen Victoria Hospital, East Grinstead, UK; 2Eye Department, Maidstone and Turnbridge Wells Hospital, Maidstone, UK; 3Research Institute of Ophthalmology, Giza, Egypt; 4Eye Department, University Hospital Basel, Basel, Switzerland*These authors contributed equally to this workCorrespondence: Mohamed ElalfyQueen Victoria Hospital, Holtye Road, East Grinstead, West Sussex, RH19 3DZ, UKTel +44 01342414560Email m.elalfy@nhs.netPurpose: To evaluate the incidence, demographics, associated risk factors, management and clinical outcomes of ocular hypertension/glaucoma after Descemet stripping automated endothelial keratoplasty (DSAEK).Methods: A cohort review of 81 DSAEK cases was performed at Queen Victoria Hospital, United Kingdom. Patients with pre-existing glaucoma, transient increased IOP within the first 48 hours post-graft, additional post-transplant surgery, or failed to complete one year follow-up were excluded from the study. Ocular hypertension was defined as intraocular pressure (IOP) elevation > 21mmHg or ≥ 6mmHg from baseline at any postoperative visit. The study looked at the incidence, risk factors, response to anti-glaucoma treatment, graft failure and best corrected visual acuity.Results: The incidence of post-DSAEK ocular hypertension and glaucoma was 51.9% and 13.6%, respectively. Steroid-induced IOP elevation was the most frequent cause, with an incidence of 38.3%. Risk factors such as pseudophakia (p=0.024) and preoperative IOP> 16 (p=0.003) were found to be associated with post-DSAEK ocular hypertension. Preoperative IOP> 16 had 5.27 times risk of IOP elevation. Eyes with graft dislocation and/or detachment were significantly associated with post-DSAEK glaucoma (p=0.038). There was no negative effect of OHT on visual acuity and graft status.Conclusion: Glaucoma and OHT are common postoperative complications of DSAEK. Although steroid-induced IOP elevation was the most frequent cause, there are other reasons associated with development of post-DSAEK glaucoma, including graft dislocation and detachment. Eyes with preoperative IOP> 16 mm Hg may require a close monitoring of IOP. In addition, management by medical treatment results in good visual acuity and graft clarity.Keywords: Descemet’s stripping endothelial keratoplasty, DSAEK, glaucoma, ocular hypertension

Marilita M Moschos,1 Eirini Nitoda,1 Irini P Chatziralli,1 Zisis Gatzioufas,2 Chryssanthi Koutsandrea,1 George Kitsos3 1First Department of Ophthalmology, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Swiss Eye Research Foundation, Orasis Eye Clinic, Reinach, Switzerland; 3Department of Ophthalmology, Medical School, University of Ioannina, Ioannina, Greece Objective: This study was conducted to evaluate the macular status of patients treated with hydroxychloroquine before and after cessation of treatment.Methods: Forty-two patients with systemic lupus erythematosus underwent ocular examination based on visual acuity evaluation, optical coherence tomography retinal thickness measurements, and multifocal electroretinography (mfERG) records at first visit. The tests were repeated 6 months after treatment withdrawal and compared to the findings at their first visit.Results: Mean visual acuity (measured in log minimum angle of resolution) of both eyes was statistically increased after hydroxychloroquine discontinuation (difference in means: 0.06 [P

Bojan Pajic,1–3 Iraklis Vastardis,1,2 Zisis Gatzioufas,1 Brigitte Pajic-Eggspuehler1 1Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland; 2Eye Hospital VIDAR-ORASIS Swiss, Department of Physics, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia; 3Medical Faculty, Military Medical Academy, University of Defense, Belgrade, Serbia Background: The purpose of this work is to report our experience using the new Z8 laser system for femtosecond laser-assisted cataract surgery (FLACS) and to provide a sample of the performance and safety results using this new technology. Methods: This prospective observational study was performed at the Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland. Fourteen patients were subjected to unilateral FLACS. Capsulotomy and lens fragmentation were performed with the aid of the LDV Z8 femtosecond laser system. Ease of phacoemulsification (on a 4-point scale), completeness of capsulotomy (on a 10-point scale), time for preparation of femtosecond laser (minutes), effective phacoemulsification time (seconds), total duration of surgery (minutes), and safety of the procedure were evaluated. Results: Ease of fragmentation and completeness of capsulotomy were estimated at 3.9 and 9.9, respectively. The preparation time for femtosecond was 3.6±0.7 minutes, effective phacoemulsification time was 2.5±3.1 seconds, and total duration of the FLACS procedure was 16.3±4.5 minutes. No major complications were observed. Approximately 42% of all patients (6/14) showed Descemet’s folds directly postoperatively. Conclusion: FLACS with the LDV Z8 system was characterized by complete capsulotomy and highly effective and reproducible lens fragmentation. The safety of the procedure was very good as perceived by the surgeon operating in this observational case series. The cost to benefit ratio should be further debated by assessing the results of a major prospective study, which is required for valid evaluation of the efficiency and safety of the LDV Z8 laser system and of FLACS in general. Keywords: femtosecond laser, cataract surgery, effective phacoemulsification time, complications

Bojan Pajic,1–3,5 Iraklis Vastardis,1,3 Brigitte Pajic-Eggspuehler,1 Zisis Gatzioufas,2 Farhad Hafezi2,4 1Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland; 2Division of Ophthalmology, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland; 3Eye Hospital VIDAR-ORASIS Swiss, University of Novi Sad, Faculty of Physics, Novi Sad, Serbia; 4Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 5Military Medical Academy, University of Defense, Belgrade, SerbiaPurpose: To compare a femtosecond laser with a microkeratome for flap creation during laser in situ keratomileusis (LASIK) in terms of flap thickness predictability and visual outcomes.Patients and methods: This was a prospective, randomized, masked, paired-eye study. Forty-four patients (34 females) who received bilateral LASIK were included. Patients were stratified by ocular dominance, and they then underwent randomization of flap creation using the femtosecond laser on one eye and undergoing the microkeratome procedure on the other one. The visual outcome differences between the corrected distance visual acuity (CDVA) at baseline and the uncorrected distance visual acuity (UDVA) on the first day postoperatively were set as the efficiency index for both groups. All visual acuity outcome results and the deviation of flap thickness were evaluated. P-values

Magdalini Triantafylla,1 Horace F Massa,2 Doukas Dardabounis,1 Zisis Gatzioufas,2 Vassilios Kozobolis,1 Konstantinos Ioannakis,1 Irfan Perente,1,3 Georgios D Panos1,21Department of Ophthalmology, University General Hospital of Alexandroupolis, School of Medicine, University of Thrace, Alexandroupolis, Greece; 2Department of Ophthalmology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland; 3Beyoglou Eye Research and Teaching Hospital, Istanbul University, Istanbul, TurkeyAbstract: Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions.Keywords: age-related macular degeneration, diabetic macular edema, retinal vein occlusion, anti-VEGF, safety, efficacy, quality of life

Georgios D Panos,1 Zisis Gatzioufas,1 Ioannis K Petropoulos,1 Doukas Dardabounis,2 Gabriele Thumann,1 Farhad Hafezi11Department of Ophthalmology, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland; 2Department of Ophthalmology, University Hospital of Alexandroupolis, GreecePurpose: To report the effect of intravitreal ranibizumab therapy for serous and vascular pigment epithelial detachments (PED) associated with choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD).Methods: In a prospective study, best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were collected for 62 eyes of 62 patients, with serous or vascular PED associated with CNV secondary to AMD. Intravitreal ranibizumab 0.5 mg was administered with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to the retreatment criteria of the PrONTO study. The change in visual acuity and PED height from baseline to month 12 after the first injection was determined.Results: Sixty-one eyes of 61 patients (one of the patients developed retinal pigment epithelial tear and was excluded from the study) were assessed at the 12-month follow-up examination. There were two types of PED, including vascular PED in 32 patients (Group A) and serous PED (Group B) in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was 0.09 logMAR (Logarithm of the Minimum Angle of Resolution) in Group A and 0.13 logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12 months after the first injection compared with the baseline value (P < 0.05). In relation to the PED height, the mean decrease of mean PED height from baseline to 12 months was 135 µm in Group A and 180 µm in Group B. Both groups showed significant reduction of the PED height during the follow-up period (P < 0.01). The PED anatomical response to ranibizumab was not correlated with the BCVA improvement in any of the groups. Apart from one patient who developed pigment epithelial tear no other complications were documented.Conclusion: Ranibizumab is an effective and safe treatment for improving vision in patients with serous and vascular PED, although the anatomical response of the PED to ranibizumab may not correlate directly with the visual outcome.Keywords: age-related macular degeneration, choroidal neovascularisation, intravitreal injection, pigment epithelial detachment, ranibizumab

Marilita M Moschos,1 Zisis Gatzioufas,2 Tryfon Rotsos,1 Chrysanthos Symeonidis,3 Xuefei Song,2 Berthold Seitz2 11st Department of Ophthalmology, University of Athens, Athens, Greece; 2Department of Ophthalmology, University of Saarland, Homburg/Saar, Germany; 32nd Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece Background: Macular edema (ME) is caused by abnormal retinal capillary permeability and has also been described as a postoperative complication of cataract surgery (Irvine-Gass syndrome). Objective: To present a patient with Irvine-Gass syndrome in the right eye complicated with a macular hole (MH) in the same eye and possible associations between these two entities. Case report: A 72-year-old male with a history of uneventful bilateral cataract surgery was followed-up with biomicroscopy and optical coherence tomography (OCT). Four weeks after cataract surgery oculus dexter (OD), there was progressive visual deterioration (best corrected visual acuity [BCVA]: 0.5). OCT disclosed cystoid ME. A parabulbar triamcinolone injection, dexamethasone 0.1% and ketorolac 0.4% eye drops, both 4 times per day OD were administered. Six weeks later (BCVA OD: 0.2), OCT revealed cystoid ME and full-thickness MH. Conclusion: ME secondary to diabetes or central retinal vein occlusion may lead to MH by inducing focal vitreomacular traction and by triggering inflammatory mechanisms which facilitate a marked thinning of the fovea. MH may occur even in cases of pseudophakic ME, representing a rare complication of Irvine-Gass syndrome. Keywords: Irvine-Gass syndrome, macular hole, macular edema