ABCA4-related retinopathies in Lebanon.

Variants in ATP-binding cassette transporter type A4 (ABCA4) have been linked to several forms of inherited retinal diseases (IRDs) besides the classically defined Stargardt disease (STGD), known collectively as ABCA4 retinopathies. ABCA4 is a sizable locus harboring 50 exons; thus, its analysis has revealed over 2,400 variants described, of which more than 2,000 are causal. Due to the clinical and genetic heterogeneity, diagnosing ABCA4 retinopathies is challenging. To date, no ABCA4-related retinopathy has been detected in Lebanon. Using next-generation sequencing, we analyzed our IRDs' cohort retrospectively (61 families) and identified five with ABCA4-related retinopathies, making it a relatively abundant cause of IRDs (about 8 %). Three families were diagnosed with rod-cone dystrophy (RCD), two with STGD, and one with cone-rod dystrophy (CRD). In conclusion, our study showed the presence of ABCA4 variants with a high degree of heterogeneity in Lebanon.

Proliferative vitreoretinopathy: a revised concept of retinal injury and response.

Previous concepts for the pathogenesis of proliferative vitreoretinopathy (PVR) have focused on the central role of retinal pigment epithelium cells only, potentially contributing to the lack of clinical advances. More recent studies have demonstrated the essential role of retinal glial cells in the PVR healing response but failed to identify a consistent triggering mechanism.We propose a revised concept for the pathogenesis of PVR based on retinal injury and response. A posterior vitreous detachment (PVD) is invariably present in patients with rhegmatogenous retinal detachment and PVR. There is evidence to suggest that the shearing forces of acute PVD can cause mechanical injury to the inner retina and trigger a subsequent intraretinal glial healing response. That response is characterised by subclinical glial cell activation and proliferation that may then be amplified into full-blown PVR by coexisting pathology such as retinal breaks and detachment.Whether a PVD causes interface pathology depends on the plane of separation of the posterior vitreous and areas of increased vitreoretinal adhesions. If the vitreous separates in a plane or location that damages the inner retina then glial cell activation and proliferation are likely to develop. The severity of the subclinical inner retinal damage may then represent one of the missing links in our understanding of the pathogenesis of PVR and would explain many of the findings we encounter in clinical practice. Controlling the process of acute PVD and subsequent intraretinal response may be essential in the prevention and management of PVR.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Is There a Link Between Vitreous Cortex Remnants and Anatomic Outcome of Vitrectomy for Primary Rhegmatogenous Retinal Detachment?

Purpose: To study the anatomic outcome of leaving vitreous cortex remnants (VCR) during pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). Methods: The study comprised patients with RRD who had PPV by a single surgeon between January 2019 and December 2020 and followed for 6 months. After intravitreal injection of triamcinolone acetonide, the topographic pattern of VCR at the periphery (p) and macula (m) was divided into 2 types by extent: complete or 4 quadrants (pVCR4Q), and between 2 and 4 quadrants ≥2 quadrants (pVCR>2Q), or by location >1 inferior retinal quadrant (pVCR>1InfQ), and at the macula (mVCR). Anatomical failure or retinal re-detachment within 6 months after surgery was the primary outcome measures. The occurrence of grade C proliferative vitreoretinopathy (PVR) and epiretinal membrane (ERM) were used as secondary outcome indicators. Results: A 6-month prospective follow-up was performed on 103 patients. pVCR4Q was detected in 31 eyes, pVCR>2Q in 40 eyes, pVCR>1InfQ in 40 eyes and mVCR in 54 eyes. Recurrent RRD developed in 9 (8.7%) eyes, PVR grade C in 6 (5.8%) eyes and ERM in 11 (10.7%) eyes. According to multivariate regression analysis, the existence of any type of VCR did not correlate with anatomical failure, PVR or ERM. Conclusion: The initial success rate of PPV and the growth of PVR or ERM do not appear to be impacted by keeping VCR.

Novel Missense and Splice Site Mutations in USH2A, CDH23, PCDH15, and ADGRV1 Are Associated With Usher Syndrome in Lebanon.

The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C > A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G > A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G > A in USH2A, and c.3999-6A > G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2-4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.

Clinical characteristics of full thickness macular holes that closed without surgery.

PURPOSE: To ascertain the anatomic factors that help achieve non-surgical sealing in full thickness macular hole (FTMH). METHODS: Retrospective collaborative study of FTMH that closed without surgical intervention. RESULTS: A total of 78 patients (mean age 57.9 years) included 18 patients with blunt ocular trauma, 18 patients that received topical or intravitreal therapies and 42 patients with idiopathic FTMH. Mean±SD of the initial corrected visual acuity (VA) in logMAR improved from 0.65±0.54 to 0.34±0.45 (p<0.001) at a mean follow-up of 33.8±37.1 months. FTMH reopened in seven eyes (9.0%) after a mean of 8.6 months. Vitreomacular traction was noted in 12 eyes (15.8%), perifoveal posterior vitreous detachment in 42 (53.8%), foveal epiretinal membrane in 10 (12.8%), cystoid macular oedema (CME) in 49 (62.8%) and subretinal fluid (SRF) in 20 (25.6%). By multivariate analysis, initial VA correlated to the height (p<0.001) and narrowest diameter of the hole (p<0.001) while final VA correlated to the basal diameter (p<0.001). Time for closure of FTMH (median 2.8 months) correlated to the narrowest diameter (p<0.001) and the presence of SRF (p=0.001). Mean time for closure (in months) was 1.6 for eyes with trauma, 4.3 for eyes without trauma but with therapy for CME, 4.4 for eyes without trauma and without therapy in less than 200 µm in size and 24.7 for more than 200 µm. CONCLUSION: Our data suggest an observation period in new onset FTMH for non-surgical closure, in the setting of trauma, treatment of CME and size <200 µm.

PREVALENCE OF VITREOUS CORTEX REMNANTS IN EYES WITH PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT UNDERGOING VITRECTOMY.

BACKGROUND/PURPOSE: To evaluate the prevalence and extent of vitreous cortex remnants (VCR) on the surface of the retina in eyes with primary rhegmatogenous retinal detachment (RRD) and posterior vitreous detachment. METHODS: Triamcinolone acetonide was injected in the vitreous cavity of 100 consecutive cases of acute primary RRD undergoing pars plana vitrectomy. A multivariate regression analysis was performed to determine any association between the presence and pattern of stained VCR on the surface of the retina and the following variables: age, diabetes, axial length, phakic status, extent of RRD, and macular status. RESULTS: Vitreous cortex remnants were found in 42 eyes. These were focal in eight eyes and diffuse in 34 eyes. Age was the only strong and independent risk factor associated with the presence of VCR (P = 0.0019). Age (P < 0.0001), axial length (P = 0.0037), and phakia (P = 0.01) were independent risk factors associated with the diffuse pattern. Neither diabetes, extent of RRD, nor macular status were significant risk factors for the presence or extent of VCR. CONCLUSION: Older patients with primary RRD and posterior vitreous detachment seem to be at a higher risk of having diffuse VCR. Further studies are needed to investigate the relevance of VCR in the pathogenesis, progression and treatment of RD.

Intraocular application of Mitomycin C to prevent proliferative vitreoretinopathy in perforating and severe intraocular foreign body injuries.

AIM: To assess the long-term anatomical and functional outcomes in addition to complications of a new surgical technique of localized intraocular application of mitomycin C (MMC) to prevent proliferative vitreoretinopathy (PVR) in eyes with open globe trauma. METHODS: Prospective non-comparative interventional case series of 16 consecutive eyes with perforating and deep choroidal impact foreign body injuries presenting over a 2-year period. Patients underwent vitrectomy with intraocular application of MMC at the site of the chorioretinal injury and were followed-up for 1 year. The primary outcome measure was the rate of postoperative PVR. Secondary outcome measures were number of vitreoretinal surgeries (VRS) required, best corrected visual acuity (BCVA), final anatomical success rate and globe survival rate (GSR). RESULTS: Patients underwent VRS at a mean time of 8.5 ± 4.6 days after the injury. Postoperative PVR developed in 2 (13 %) eyes and required only one additional VRS each. One other eye underwent further peeling of an epimacular membrane. BCVA improved from mean LogMAR 3.08 ± 0.72 preoperatively to 0.66 ± 0.79 at 1 year. All 10 eyes without a macular injury had a final BCVA of LogMAR 0.40 or better. The final anatomical success rate was 94% and GSR rate was 100%. There were no complications related to the intraocular use of MMC. CONCLUSIONS: Vitrectomy and intraocular application of Mitomycin C may have a potential role in reducing the rate of post traumatic PVR and improving anatomical and functional outcomes in eyes with perforating and deep choroidal impact foreign body injuries.

Novel Missense Mutations in BEST1 Are Associated with Bestrophinopathies in Lebanese Patients.

To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.

Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet-Biedl and Usher Syndromes.

AIM: To identify disease-causing mutations in four Lebanese families: three families with Bardet-Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). METHODS: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. RESULTS: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. CONCLUSION: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders.

Retinal detachment in albinism.

PURPOSE: To report the visual and anatomic outcomes of albino retinal detachment (ARD) repair. METHODS: Collaborative retrospective analysis of ARD. Outcome measures were number of surgical interventions, final retinal reattachment, and best corrected visual acuity (BCVA) at last follow-up. RESULTS: Seventeen eyes of 16 patients (12 males; mean age =37.8 years) had the following complications at presentation: macula off (14), total (7) or inferior detachment (5), proliferative vitreoretinopathy (5), detectable break (16), lattice (5), horseshoe tears (9), and giant tear or dialysis (4). Mean number of interventions was 1.8 (range =1-5) and included cryopexy (15) with scleral buckle (11), and/or vitrectomy (8). Mean initial BCVA was counting finger (CF) 1 m and at last follow-up (mean 77 months) CF4m with mean improvement of 4.5 lines (early treatment diabetic retinopathy study) (P=0.05). Intraoperative choroidal hemorrhage occurred in three eyes. The retina was finally attached in 14 eyes, with residual inferior detachment in three eyes with silicone oil in situ. Silicone oil was kept in six of seven eyes because of residual inferior detachment (3) and removal of silicone oil, which led to redetachment (1) or fear of redetachment (2). CONCLUSION: Repair of ARD may require several interventions, with the need to keep silicone oil in several cases due to nystagmus and reduced melanin pigment.

ENDOILLUMINATION-ASSISTED MODIFIED SCLERAL BUCKLING.

PURPOSE: To assess the anatomical and functional outcomes in addition to complications for endoillumination-assisted modified scleral buckling surgery using a noncontact Oculus BIOM wide-angle viewing system in patients with primary rhegmatogenous retinal detachment. METHODS: This is an interventional prospective noncomparative case series. Consecutive patients listed for scleral buckle surgery for primary rhegmatogenous retinal detachment were enrolled over an 18-month period and followed up for 1 year. The study cohort consisted of 25 patients (25 eyes) of which 23 patients (23 eyes) completed the 1-year follow-up. Scleral buckling surgery was done with a 23-gauge endoillumination probe, which was inserted through a pars plana sclerotomy. The primary outcome measure was anatomical success rate with one surgery assessed at the 6-month and the 1-year follow-up. Secondary outcome measures included final visual acuity, number of surgeries required, and complication rates such as entry site break, posterior vitreous detachment, endophthalmitis, and cataract. RESULTS: At 1 year, anatomical success with one surgery was achieved in 20 patients (87%). One patient required two additional vitreoretinal surgeries and 2 patients required three additional surgeries. All patients had a flat retina at 1 year with silicone oil present in one eye. Mean best-corrected visual acuity improved by six ETDRS lines, from 1.03 ± 0.83 logarithm of the minimum angle of resolution (20/200) preoperatively to 0.40 ± 0.47 logarithm of the minimum angle of resolution (20/50) at 1 year. No entry site breaks were detected, and posterior vitreous detachment developed in six patients (26%). No cases of endophthalmitis or cataract progression were reported. CONCLUSION: Endoillumination-assisted modified scleral buckling surgery combined with a noncontact wide-angle viewing system can provide good anatomical and functional outcomes with many advantages and a low complication rate.

Combined lensectomy, vitrectomy, and primary intraocular lens implantation in patients with traumatic eye injury.

PURPOSE: To analyse the postoperative anatomic and functional outcomes in addition to complications after combined lensectomy, vitrectomy, and primary intraocular lens (IOL) implantation in patients with traumatic eye injury. METHODS: Retrospective review of patients with traumatic cataract and posterior segment injury who underwent combined lensectomy, vitrectomy, and primary IOL implantation with a minimum follow up (FU) of 3 months. RESULTS: Thirteen consecutive patients (all male) with a mean age of 42.8 years (range 17-82 years) underwent combined lensectomy, vitrectomy, and primary IOL implantation from February 2000 to January 2006. Postoperative FU ranged from 3 to 54 months (mean 17.6 months). Best corrected visual acuity (BCVA) at presentation ranged from 20/30 to hand movement and was worse than 20/200 in eight patients (61%). Four patients (31%) had blunt trauma with no globe rupture. Of the nine patients (69%) with a penetrating eye injury (PEI), eight had an intraocular foreign body (IOFB) with one retinal detachment at presentation. Four patients had primary closure at the time of the vitrectomy. All eight IOFBs were removed. Seven patients had additional scleral buckling and four intravitreal gas injection. BCVA at last FU ranged from 20/20 to 20/300 and was 20/40 or better in eight eyes (62%). All patients had an attached retina at last FU. One eye had further surgery for epiretinal membrane proliferation and ptosis. CONCLUSIONS: These results suggest that combined vitrectomy, lensectomy and primary intraocular implantation can offer good visual rehabilitation in patients with traumatic cataract and posterior segment injury.