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Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy., Competing Interests: Diana Do reports grants from and consultancy for Regeneron during the conduct of the study and grants from and advisory board for Genentech outside the submitted work. Quan Dong Nguyen reports grants and personal fees from Genentech, Novartis, and Regeneron, and personal fees from Rezolute, outside the submitted work. The authors report no other potential conflicts of interest in relation to this work., (© 2022 Ghoraba et al.)

Purpose: To evaluate the safety of intravenous high-dose pulse methylprednisolone succinate (IVHDM) in the management of severe or refractory non-infectious pediatric uveitis., Methods: We reviewed all uveitis patients who were ≤16 years of age and who received IVHDM with a dose of ≥500 mg per day (1-3 days a month) for at least 3 months during their management at a tertiary care eye hospital., Results: Twenty pediatric patients with severe or refractory uveitis who received IVHDM were identified. Six patients received IVHDM either once, as a preoperative medication, or at a lower dose than 500 mg, and were excluded. The remaining 14 patients received IVHDM for at least 4 months. Age (mean±SD) was 11.9±2.4 years and 50% were female. Duration of treatment was 14.2±7.5 months. Thirteen patients received IVHDM in combination with other immunomodulatory therapy (IMT). Except for two outliers, IVHDM was given at a dose of 8-25 mg/kg per infusion. Three major adverse events (AEs) occurred in two patients: a single episode of bradycardia, compression fracture following minor trauma and adrenal insufficiency. The number of AEs (major and minor) strongly correlated with duration of treatment ( p =0.004) and moderately correlated with the cumulative dose/weight ( p =0.051). Weight gain was associated with the use of concomitant oral steroids and not with duration of treatment or cumulative dose., Conclusion: IVHDM may be a valid therapeutic option for aggressive/refractory pediatric uveitis. The reported AEs in this series can also be attributed to the concurrent IMT or the underlying disease itself., Competing Interests: Prof. Dr. Diana Do reports grants and personal fees from Regeneron, and personal fees from Genentech, outside the submitted work. Prof. Dr. Quan Dong Nguyen reports grants and personal fees from Genentech, personal fees from Bausch and Lomb, grants and personal fees from Regeneron, grants and personal fees from Novartis, and grants and personal fees from Santen, outside the submitted work. The authors report no conflict of interest in this work., (© 2022 Ghoraba et al.)

Purpose: To report the long-term outcome of pars plana vitrectomy (PPV) for management of retained posterior segment intraocular foreign body (IOFB) secondary to gunshot injury., Methods: This is a retrospective interventional case series including consecutive patients who had PPV for retained posterior segment IOFB secondary to gunshot injury. Main outcome measures were final best-corrected visual acuity (BCVA), long-term globe survival and detection of complications. Spearman correlation analyzed relationships between numerical data. Kruskal-Wallis test compared differences in initial BCVA and final BCVA across variables. Categorical variables were tested using Chi square or Fisher's exact test. P value is significant at 0.05., Results: The study included 103 eyes of 103 patients. Mean baseline BCVA was 0.01 decimal unit (2 logMAR). Mean duration from primary repair to PPV was 3 weeks. Mean duration of post-operative follow-up was 60 months. Mean final BCVA was 0.04 decimal unit (1.3 logMAR), p 0.001. Post-operatively, BCVA improved in 58.2% of patients. Nineteen patients (18%) gained ≥2 lines of vision, and 15 patients (14.5%) achieved final BCVA of 0.4 decimal unit (logMAR 0.4). All complications were related to the original injury. These included macular scar (19%), macular pucker (6%), recurrent retinal detachment (4%), subretinal fibrosis (3%), consecutive optic atrophy (3%), and PVR (3%). Phthisis bulbi or sympathetic ophthalmia did not develop in any case., Conclusion: PPV for removal of IOFB caused by gunshot injury yielded long-term favorable functional outcome with excellent globe survival. Poor initial BCVA, location of IOFB in the posterior pole, associated lens injury and retinal detachment are significant adverse prognostic factors for final BCVA but not for globe survival., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Ghoraba et al.)

Purpose: To assess the efficacy of pars plana vitrectomy (PPV) and silicone oil tamponade for management of myopic retinal detachment associated with macular hole (MRDMH) and to assess the anatomical and functional outcomes of this technique and its long-term validity after silicone oil removal., Methods: Retrospective interventional non-comparative case series including consecutive patients who had PPV and silicone oil tamponade for MRDMH. All patients had an axial length ≥26 mm. Main outcome measures were retinal re-attachment and macular hole closure after silicone oil removal, improvement of best-corrected visual acuity (BCVA), and complications secondary to surgery. Chi square/Fisher's exact test was used to analyze categorical variables, while One-way ANOVA/Kruskal-Wallis test was used to compare variables across the closure type and complications. Correlations between numerical variables were tested using Spearman correlation. Kaplan-Meier method was used to estimate the event-free survival. P value is significant at 0.05., Results: The study included 26 eyes of 26 patients. Retinal re-attachment rate after primary and secondary surgeries was 88.4% and 100%, respectively. W-type macular hole closure occurred in 58% of eyes. Vision improved in 58% of eyes. Mean final BCVA was 0.05 decimal units, p = 0.004. Cataract and glaucoma developed in 42% and 15% of eyes, respectively. Initial BCVA, axial length and duration of silicone oil tamponade did not correlate significantly with either the type of macular hole closure or the final BCVA., Conclusion: PPV and silicone oil tamponade technique promotes successful anatomical and functional outcome in MRDMH. Long-term success is maintained after silicone oil removal. High incidence of silicone oil-induced complications mandate its removal from eyes with successful retinal re-attachment., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Ghoraba et al.)

Purpose: To compare different types of macular holes regarding the anatomic and functional success following pars plana vitrectomy (PPV) and internal limiting membrane (ILM) removal., Methods: A retrospective review of all patients with macular holes treated by PPV, ILM removal with gas tamponade from January 2014 to July 2017 in Magrabi Eye Hospital., Results: One hundred fifty-seven eyes of 153 patients were analyzed. The eyes were classified according to the etiology of macular hole into four groups: 79 eyes with idiopathic macular hole (IMH), 51 eyes with traumatic macular hole (TMH), 16 eyes with macular hole in diabetic patients (DMH) and 11 eyes with myopic macular hole (MMH). We classified the IMH group based on the International Vitreomacular Traction Study Classification according to size into 3 subgroups; subgroup 1: ≤250µ, subgroup 2: >250 to 400µ and subgroup 3: ≥400 µ. All types of macular hole showed statistically significant postoperative improvement in BCVA compared to the baseline except cases with MMH. Anatomic postoperative hole closure was achieved in 86.1%, 60.7%, 43.65%, an 45.46% of eyes with IMH, TMH, DMH and MMH, respectively. In eyes with IMH, closure rate in subgroup 1 was significantly higher than in subgroups 2, and 3., Conclusion: PPV, ILM peel and C2F6 technique yielded variable anatomic and functional outcomes in different types of macular holes. Anatomic results were most favorable in IMH and least favorable in MMH. The smaller the diameter of the hole the better the results. The underlying pathogenetic mechanisms that lead to different types of macular holes are pivotal in determining the final outcome., Competing Interests: This work was self-funded by the authors. The authors report no conflicts of interest for this work., (© 2021 Ghoraba et al.)

Background and Objectives: To compare anatomical and visual results of pars plana vitrectomy (PPV) with or without additional encircling band in the management of pediatric traumatic rhegmatogenous retinal detachment (RD) in a tertiary referral center., Methods: A retrospective review of children diagnosed with traumatic rhegmatogenous retinal detachment treated by pars plana vitrectomy with or without encircling band., Results: One hundred thirty-nine eyes of 139 children diagnosed with traumatic rhegmatogenous retinal detachment. Surgeries were performed between May 2011 and November 2016. Patients were followed up for at least 18 months after last intervention. The included eyes were categorized into two groups. Group A (vitrectomy with additional encircling band) included 72 eyes of 72 children; 58 boys and 14 girls. Group B (vitrectomy without encircling band) included 67 eyes of 67 children; 58 boys and 9 girls. In group A, the mean age was 9.21±3.24. Attached retina was achieved in 61% (44 out of 72 eyes), of which 34 eyes remained attached after silicon oil removal, and 10 eyes remained attached under silicon oil tamponade. Recurrent RD under oil was present in 28 eyes (38.9%). In group B, the mean age was 11.06±3.64. Attached retina was present in 61.2% (41 out of 67 eyes), of which 30 eyes remained attached after oil removal, and 11 eyes remained attached under silicon oil tamponade. Recurrent RD was present in 26 eyes (38.8%). In group A, the final visual acuity (VA) ranged from NLP to 0.5; 58.7% of patients achieved VA more than counting fingers at 1 meter, and 34.6% of patients achieved VA of 0.05 or more. In group B, the final postoperative VA ranged from NLP to 0.9; 16% of patients achieved VA from counting fingers at 1 meter to 0.05, and 29.2% achieved VA of 0.05 or more., Conclusion: Although no statistically significant difference between the two groups (combined vitrectomy and encircling band versus vitrectomy alone in pediatric traumatic retinal detachment), it is wise to consider adding encircling band in severe trauma cases., Competing Interests: The authors have not received grant support or research funding and they do not have any proprietary interests in the materials described in the article., (© 2020 Ghoraba et al.)

Objective: To describe the optical coherence tomography (OCT) findings in terms of macular hole closure and ellipsoid zone (EZ) recovery following modified internal limiting membrane (ILM) surgical technique in traumatic macular holes (TMH)., Methods: The study was a retrospective case series that recruited 16 consecutive patients with TMH. Following vitrectomy (PPV), we performed modified ILM surgical technique (IFT) in which ILM peel was stopped at the edges of the hole forming a floating ILM flap. Primary outcome measures were pattern of TMH closure and recovery of EZ. Student's T -test and Pearson's correlation coefficient were used for statistical analysis., Results: The study had 16 eyes of 16 patients. Mean baseline minimum linear diameter (MLD) was 562µ. Mean baseline best-corrected visual acuity (BCVA) was 1.4 logMAR. U-pattern closure occurred in 50% of eyes, V-pattern closure occurred in 31.2% of eyes, whereas W-pattern closure occurred in 18.7% of eyes. Mean BCVA improvement was 5 lines (p 0.02). Failure of recovery of EZ was detected in 75% of eyes. In the present series, neither pre-operative MLD nor time lapse prior to surgery were significant factors in determining the closure pattern of TMH, the grade of EZ recovery or final BCVA., Conclusion: Modified IFT is effective in promoting macular hole closure and improving visual acuity in patients with TMH. The technique does not promote recovery of EZ., Competing Interests: The authors declare no conflicts of interest regarding the publication of this article. The authors did not receive funding from any institution in support of this publication., (© 2019 Ghoraba et al.)

Purpose: The purpose of this study was to evaluate the safety of high-dose intravitreal triamcinolone acetonide (IVTA) as affordable low-cost alternative to anti-vascular endothelial growth factor (anti-vascular endothelial growth factor [anti-VEGF] agents) in lower-middle-income countries., Patients and Methods: This was a retrospective interventional non-comparative case series. The study recruited patients who received 20 mg IVTA for treating various retinal and optic nerve diseases over the past 5 years. Main outcome measure was assessment of complications secondary to high-dose IVTA. The crosstabs procedure was used to display the interaction between the variables tested. The ANOVA test was used to analyze the differences among group means., Results: The study included 207 eyes of 168 patients. The main indication for high-dose IVTA were diabetic macular edema 64%, and macular edema secondary to retinal vein occlusion 19%. The mean follow-up period post-injection was 22 months. Mean number of injections was 1.3. Cataract developed in 54% of eyes. Glaucoma developed in 18.5% of eyes. Glaucoma surgery for intractable glaucoma attributed to high-dose IVTA was needed in 1% of eyes. Endophthalmitis and retinal detachment developed in one patient each., Conclusion: High-dose IVTA is a safe and cost-effective alternative to anti-VEGF agents. Cataract formation and intraocular pressure rise do not pose major adverse effects when weighed against the risk of vision loss due to inability to afford anti-VEGF treatment., Competing Interests: Disclosure The manuscript discusses the use of high-dose IVTA as alternative to anti-VEGF agents. Currently, high-dose IVTA is used as an off-label ocular therapeutic agent that is not approved by the US Food and Drug Administration. The authors report no conflicts of interest in this work.

Objective: The aim of this study was to report and compare the anatomic and functional results of primary vitrectomy with and without 360° encircling scleral buckle (SB) for the treatment of rhegmatogenous retinal detachment (RRD) due to inferior retinal break(s)., Background: A variety of options, including SB, pars plana vitrectomy (PPV) with or without SB, and pneumatic retinopexy have been described as methods to repair RRDs. The use of additional SB with vitrectomy for RRD associated with inferior breaks has been a recent controversy after the introduction of transconjunctival cannula systems., Patients and Methods: A retrospective, interventional, comparative case study was performed. In this study, we reviewed 105 consecutive patients who underwent vitrectomy for primary RRD with inferior retinal break(s) at the vitreoretinal center, performed by a single surgeon. Ninety four patients (94 eyes) were followed up for at least 4 months after silicon oil removal (SOR), and were analyzed. They were divided into two groups: group I included 50 patients who underwent PPV alone + silicon oil (SO); and group II included 44 patients who underwent PPV with 360° SB + SO. The essential parameters were single-operation success rate (SOSR) before SOR, incidence of retinal redetachment after SOR, and final visual acuity., Results: SOSR was obtained in 89 eyes (47 [94%] in group I and 42 [95.5%] in group II). From overall 59 phakic retinal detachments (RDs), SOSR was obtained in 56 eyes (30 in group I [93.8%] and 26 in group II [96.3%]) while from overall 35 aphakic or pseudophakic RDs, SOSR was obtained in 33 eyes (17 in group I [94.4%] and 16 in group II [94.1%]). Retinal redetachments after SOR occurred in three patients in group I and two patients in group II. Visual acuity improvement was greater in group I than in group II before SOR., Conclusion: Both surgical procedures had similar reattachment rates. The addition of 360° SB to PPV + SO might not have additional benefits in patients with RD due to inferior retinal break.

Purpose: To report a retrospective series of seven phakic eyes of seven patients suffering from a malignant glaucoma-like syndrome following pars plana vitrectomy and silicone oil (SO) injection., Materials and Methods: Seven eyes with retinal detachment treated with pars plana vitrectomy with or without scleral buckling with SO tamponade. This was followed by cataract extraction to manage the elevated intraocular pressure (IOP)., Results: This was a retrospective review of seven cases that received pars plana vitrectomy and SO with or without scleral buckling for different causes of retinal detachment (three were rhegmatogenous and four were tractional). After a period ranging from 1 week to 1 month, they presented with malignant glaucoma-like manifestations; high IOP, shallow axial anterior chamber, and remarkable decrease of visual acuity. Atropine eye drops and anti-glaucoma medical treatment (topical and systemic) had been tried but failed to improve the condition. Dramatic decrease of IOP and deepening of the axial anterior chamber was observed in all cases in the first postoperative day after phacoemulsification and posterior chamber foldable intraocular lens implantation with posterior capsulotomy., Conclusion: Aqueous misdirection syndrome may be observed following pars plana vitrectomy and SO tamponade. This must be differentiated from other causes of post vitrectomy glaucoma. Cataract extraction with posterior capsulotomy controls the condition.

Purpose: To evaluate the safety and efficacy of different methods of transconjunctival cannulated vitrectomy versus conventional non-cannulated vitrectomy in various vitreoretinal disorders., Methods: A prospective randomized study was done from August 2009 to February 2011. The study included 129 eyes of 122 patients, randomly divided into four groups. Group 1 comprised 34 eyes operated on using transconjunctival 20-gauge cannula Claes system. Group 2 comprised 32 eyes operated on using transconjunctival cannulated 23 gauge system. Group 3 comprised 27 eyes operated on using combined 20-gauge non-cannulated and 23-gauge transconjunctival cannulated system. Group 4 comprised 36 eyes operated on using conventional non-cannulated 20-gauge system., Results: The four groups were demographically similar. Anatomical outcome was achieved in all cases. Vision was improved in 29 eyes (85.3%) in group 1, 23 eyes (71.9%) in group 2, 19 eyes (70.4%) in group 3, and 26 eyes (72.2%) in group 4. There was no statistical difference between the four groups 1-day postoperative (P=0.405) and 1-week postoperative intraocular pressure (P=0.254). The number of sutureless sclerotomies was 68 (66.6%) in group 1, 78 (81.3%) in group 2, 50 (61.8%) in group 3, and 0 in group 4. Hypotony occurred in one eye (2.9%) in group 1, three eyes (9.4%) in group 2, two eyes (7.4%) in group 3, and no eyes in group 4. Operative endophthalmitis did not occur in any one of the four groups., Conclusion: Final anatomical and functional outcomes were not related to the type of sclerotomy used (cannulated or non-cannulated), the gauge used (20 or 23), the route (transconjunctival or transscleral), or type of suture used. The advantages of small-gauge transconjunctival vitrectomy were patient comfort, early ambulation, and preservation of the conjunctiva. This should be weighed against the cost of this cannula system.

Purpose: To compare the effectiveness of pars plana vitrectomy (PPV) with either silicone oil or gas tamponade for the treatment of traumatic macular holes., Methods: A retrospective comparative study included 22 patients who were operated on by PPV for repair of traumatic macular holes with either silicone oil tamponade (nine patients) or perfluoropropane (C(3)F(8)) gas tamponade (13 patients)., Results: Twenty-two cases were reviewed to assess the anatomical and visual outcomes of surgery with silicone oil tamponade in nine cases (40.9%) vs 14% C(3)F(8) gas tamponade in 13 cases (59.1%). The age of the silicone oil-treated patients ranged from 10 to 40 years (mean 27.4 ± 11.3 years), while that of the gas-treated patients ranged from 19 to 35 years (mean 26.54 ± 5.68 years). Female patients accounted for 33.3% of the silicone oil group and 30.77% of the gas-treated group. The minimal follow-up time for the silicone oil-treated group was 13 months, with a maximum of 18 months after silicone oil removal. The minimal follow-up time for the gas-treated group was 12 months and the maximum was 24 months. The rate of hole closure after the primary operation with oil tamponade was significantly lower than that with gas tamponade (66.67% vs 92.3%; P = 0.022). With re-operations, the final rate of hole closure was higher in the gas group (100%) than in the silicone oil group (77.8%). The final postoperative decimal visual acuity for the gas group was significantly better than for the oil group (0.433 vs 0.245; P = 0.047)., Conclusions: C(3)F(8) gas was a more effective tamponade than silicone oil in achieving initial closure of traumatic macular holes. Eyes receiving an oil tamponade required significantly more re-operations to achieve hole closure than did eyes undergoing a gas tamponade. Final visual acuity was better for gas-treated eyes than for silicone oil-treated eyes.