Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool.

Purpose: To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool. Methods: Two UK NHS Trusts - Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) - prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects. Results: A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9-94 years) were assessed across various etiologies for an average of 24.0±14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm2 per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm2 per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06±0.51 logMAR). Conclusion: Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.

Simulation-based training for intraoperative posterior capsule rupture management: an analysis of nontechnical skills development and the relationship between technical and nontechnical skills.

OBJECTIVES: To analyse development of individual nontechnical skills (NTS) domains after undertaking a previously developed simulation-based training model and analyse the relationship between technical skills (TS) and NTS in ophthalmic surgery. METHODS: The simulation-based training model involved a cataract surgery case complicated by intraoperative posterior capsule rupture. Cataract surgeons underwent the simulation twice, separated by a training intervention. Two blinded independent experts assessed participants' NTS using HUFOES, NOn-Technical Skills for Surgeons (NOTSS), and the OSATS global rating scale for TS. Paired t-tests assessed differences in individual NTS domains, with p < 0.05 indicating significance. The Pearson Product Moment Correlation Coefficient was used to assess the correlation between scores from each scoring system. RESULTS: All NTS domains within HUFOES and NOTSS demonstrated statistically significant improvements secondary to the training intervention. Positive correlations were demonstrated between HUFOES and OSATS scores in the pre- and post-training simulations, r = 0.870 (p < 0.001) and r = 0.861 (p < 0.001), respectively. Positive correlations were also demonstrated between NOTSS and OSATS scores in pre- and post-training simulations, r = 0.849 (p < 0.001) and r = 0.757 (p = 0.001), respectively. Positive correlations were demonstrated between HUFOES and NOTSS scores; r = 0.979 (p < 0.001) (n = 17) and r = 0.959 (p < 0.001) for pre- and post-training simulations, respectively. CONCLUSION: All NTS domains contained within HUFOES and NOTSS demonstrated significant increases following the completion of the simulation-based training model. Positive correlations exist between an ophthalmic surgeon's TS and NTS. This is the first study to report these findings within ophthalmic surgery.

Non-technical skills simulation-based training model for managing intraoperative posterior capsule rupture during cataract surgery.

OBJECTIVES: To develop and implement a simulation-based training model for the management of posterior capsule rupture (PCR) from a non-technical skills (NTS) perspective, and analyse changes in participant's NTS and technical skills (TS). METHODS: The simulation-based training model consisted of two identical PCR simulations with NTS stressors applied, separated by a predominantly NTS focussed training intervention. Participants' TS and NTS were evaluated by two blinded assessors using the Objective Structured Assessment of Technical Skill (OSATS) global rating scale and the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES) respectively. Paired t-tests were used to establish the difference in mean HUFOES and OSATS scores between initial and repeat simulations; p < 0.05 indicated statistical significance. McGaghie's model of translational outcomes for simulation-based learning was used to establish the simulation model's educational status. RESULTS: Seventeen cataract surgeons of varying training grades participated in the simulation-based training model. NTS improved with statistical significance; mean HUFOES scores increased from 48.7 ± 16.6 to 59.2 ± 14.8 (p < 0.001). Mean OSATS scores increased without statistical significance from 16.0 ± 7.3 to 17.9 ± 8.3 (p = 0.07). This simulation model achieved Level 1 (internal acceptability) and Level 2 (contained effects) according to McGaghie's model. CONCLUSIONS: This novel simulation-based training model was designed to improve the NTS required for managing intraoperative PCR, through the provision of an interactive training session. Statistically significant improvements in participants' NTS in combination with statistically insignificant improvements in TS demonstrate that the simulation-based training model has specificity within the NTS domain.

Clinical outcomes after intracorneal ring segment implantation for keratoconus management in corneas with mild apical haze.

PURPOSE: The implantation of intracorneal ring segments represents an effective and safe therapeutic option for visual improvement in patients with keratoconus. The presence of corneal opacities is considered an exclusion criterion for this operation. METHODS: This is a retrospective cohort study of six eyes of six keratoconus patients at Queen Victoria Hospital, East Grinstead, UK, between January 2012 and December 2016. Femtosecond laser-assisted intracorneal ring segment implantation was performed in six eyes with apical corneal haze. Preoperative and postoperative visual acuity, keratometry readings, as well as corneal pachymetry were compared at 6-month follow-up. RESULTS: Uncorrected visual acuity (UCVA) [LogMAR] improved significantly from median 1.05 [95% confidence interval (CI): 0.83-0.13] preoperatively to 0.9 (95% CI: 0.63-1.00) at 6 months postoperatively (p = 0.03). Corrected visual acuity (CDVA) also improved significantly from median 0.75 (95% CI: 0.43-1.00) preoperatively to 0.4 (95% CI: 0.23-0.50) at 6 months postoperatively (p = 0.03). Keratometric readings, K-max (diopters) and K-mean (diopters), decreased significantly from 54.5 and 47.85 preoperatively to 53.45 and 46.42 postoperatively, respectively (p = 0.03). Corneal pachymetry showed no significant changes postoperatively. CONCLUSION: The results of this study show that the presence of apical haze should not exclude the implantation of intracorneal ring segments in patients with keratoconus.

Management of Persistent Corneal Epithelial Defects with Human Amniotic Membrane-derived Dry Matrix.

OBJECTIVE: To report the outcomes of using human amniotic membrane-derived dry matrix (AMDDM) in the management of persistent corneal epithelial defects (PEDs) of various etiologies. METHODS: A cohort study of 84 patients age range 7 to 92 years with 93 PEDs were treated with AMDDM (Omnigen® using OmniLenz® at two centers (Queen Victoria Hospital and Maidstone Hospital) in the UK. The main outcome measures were healing response of PED and time to heal after application of AMDDM. RESULTS: A total of 106 applications of AMDDM were recorded for 81 patients (52 males, 29 females) with a spectrum of different etiologies. Fifty-eight percent of the eyes showed complete healing, and 28% showed partial decrease of the size of PEDs with average treatment length recorded as 22.4±12.3 days. In patients with limbal stem cell deficiency (n=44; aniridia=12, chemical injury=9, Stevens-Johnson syndrome=10), 50% of PEDs showed complete healing and 27% showed partial healing. In patients with microbial keratitis (n=21) (bacterial: 13, fungal: 4, herpetic: 3, acanthamoeba: 1) 57% of PEDs showed complete healing and 33% were partially healed. In patients with keratoplasty (n=16), 56% of PEDs showed complete healing and 31% were partially healed. Vision remained stable in 59% and improved in 27% of the study the population. CONCLUSION: AMDDM can be easily applied in the clinical setting and has demonstrated its efficiency as a new tool to treat persistent epithelial defects.

Functional and Structural Changes Following Corneal Neurotisation in the Management of Neurotrophic Keratopathy: UK Single Centre Series.

OBJECTIVE: To report the functional and anatomical outcomes including structural changes in corneal nerve density and morphology using in vivo confocal microscopy (IVCM) after corneal neurotisation in patients with neurotrophic keratopathy (NK), using a sural nerve graft. PATIENTS AND METHODS: Prospective study of patients undergoing corneal neurotisation for NK. Functional outcomes were measured through visual acuity, slit-lamp examination of corneal and conjunctival staining, tear production (Schirmer's 1 test), tear film break-up time, tear film meniscus height, quality and osmolarity, central corneal thickness and corneal sensation using Cochet-Bonnet esthesiometry. Structural outcomes were assessed from changes in corneal nerve density and morphology with IVCM. Subjective outcomes were assessed using VFQ-25 and latest telephonic consultation. RESULTS: Between February 2016 and April 2018, 11 corneal neurotisations were performed on 11 patients (3 males, 8 females). Median age was 43 (range 25-62) years. Mean follow-up was 14.5 (range, 4-36) months. Snellen visual acuity improved in 6 patients, corneal and conjunctival staining decreased in 10, tear film breakup time increased in 9, tear meniscus height increased in 7, Schirmers test readings increased in 4, tear film osmolarity reduced in 8 and central corneal thickness increased in 10 patients. Corneal sensation improved in nine patients. Complete IVCM data were available in five cases and demonstrated an improvement of corneal nerve density and length at 12 months. CONCLUSION: This series confirms the fact that the outcomes of this technique are reproducible and that corneal neurotisation surgery helps restore trophic nerve function more consistently than touch-related sensation.

Incidence and Risk Factors of Ocular Hypertension/Glaucoma After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: 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.

Validity of scoring systems for the assessment of technical and non-technical skills in ophthalmic surgery-a systematic review.

Evaluation and recommendation of the scoring systems for technical skills (TS) and non-technical skills (NTS) assessments in ophthalmic surgery. A literature search was performed between December 2019 and May 2020. Studies describing the development or validation of TS or NTS scoring systems in ophthalmic surgery were included. Only scoring systems for completion by hand were included. The primary outcome was the validity and reliability status for each scoring system. The secondary outcome was recommendation based on modified Oxford Centre for Evidence-Based Medicine guidelines. Nineteen and five scoring systems were identified for TS and NTS respectively. TS scoring systems exist for cataract surgery (including the steps of phacoemulsification and paediatric cataract surgery) ptosis, strabismus, lateral tarsal strip, vitrectomy, and intraocular surgery in general. NTS scoring systems apply to cataract surgery or ophthalmic surgery in general. No single scoring system satisfied all validity and reliability measures. The recommended TS scoring systems are 'International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubrics' (ICO-OSCAR) for phacoemulsification, strabismus and paediatric cataract surgery, and 'Objective Structured Assessment of Cataract Surgical Skill' (OSACSS). Non-Technical Skills for Surgeons (NOTSS), Observational Teamwork Assessment for Surgery (OTAS) and Anaesthetists Non-Technical Skills (ANTS) are recommended for NTS. There is a paucity of NTS scoring systems. Further research is required to validate all scoring systems to consistent standards. Limitations of the assessment tools included infrequent quantification of face and content validity, and inconsistency in terminology and statistical methods between studies.

Development of the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES) for non-technical skills in cataract surgery.

BACKGROUND: Nontechnical skills (NTS) are fundamental for successfully managing intraoperative complications. We aimed to develop the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES); an NTS assessment system for posterior capsule rupture (PCR) during cataract surgery. METHODS: A literature review and a focus group consisting of three cataract surgeons and one NTS researcher elicited the important NTS for the management of intraoperative cataract surgery complications. A novel taxonomy of NTS specific for PCR management was generated. Questionnaires were distributed to ophthalmologists in one UK training region. Delphi methodology was used to develop a final HUFOES draft. One further questionnaire was used to gain feasibility, educational impact and validity data. RESULTS: All HUFOES components achieved a mean importance rating of >8/10 and achieved high interrater agreement ratings (α = 0.953). Interrater agreement scores for HUFOES categories were: teamwork and communication (α = 0.819), leadership (α = 0.859), decision making (α = 0.753), situational awareness (α = 0.840) and professionalism (α = 0.890). In all, 92.8% (n = 13) rated HUFOES as specific for use, 85.7% (n = 12) agreed it contains appropriate assessment measures, 92.8% (n = 13) agreed that training with HUFOES would enhance preparation for PCR management and 78.6% (n = 11) declared HUFOES as the preferable training system for NTS in intraoperative ophthalmic emergencies when compared with the current gold standard. CONCLUSIONS: HUFOES has been developed and validated as a tool for the training and assessment of NTS in PCR. An NTS training programme integrated with HUFOES should be considered in order to enhance surgical NTS for managing intraoperative complications, and improve performance and outcomes following PCR.

Influence of Perfluorocarbon Liquids on Peripapillary Retinal Nerve Fiber-Layer Thickness Following Pars Plana Vitrectomy with Silicone Oil-Based Endotamponade.

BACKGROUND: Inner retina-layer modifications after pars plana vitrectomy (PPV) can be objectively assessed through spectral domain optical coherence tomography (SD-OCT). METHODS: This study explored prospectively changes in retinal nerve-fiber layer (RNFL) thickness with SD-OCT in eyes undergoing PPV with silicone oil-based tamponade with and without use of perfluorocarbon liquids (PFCLs) during the early postoperative phase (up to 3 months) at the Research Institute of Ophthalmology, Egypt. RESULTS: Thirty patients were recruited who underwent PPV and silicone oil-based tamponade for either retinal detachment or diabetic retinopathy between April 2019 and September 2019. Mean RNFL thickness showed no significant change during follow-up at the first week (102.90±30.68 mm), 1 month (107.30±32.27), or three months (105.90±36.68; p=0.46, 0.68). There were significant correlations noticed between RNFL thinning and axial length of eyes, intraocular pressure, and use of PFCLs during the follow-up period. CONCLUSION: The RNFL tends to change postvitrectomy, but not significantly. Careful examination and consistent follow-up is required for postvitrectomy patients with larger axial length and intraoperative PFCL use.

Functional and Structural Outcomes at the Foveal Avascular Zone with Optical Coherence Tomography Following Macula off Retinal Detachment Repair.

BACKGROUND: Visual recovery following macula involving rhegmatogenous retinal detachment remains poorly understood. The aim of this work is to correlate the functional and the anatomical changes in retinal vasculature in the foveal avascular zone using optical coherence tomography angiography (OCTA) after successful retinal reattachment repair and correlate this data with retinal thickness and post-operative visual recovery. METHODS: A prospective, comparative observational study of 28 eyes of 14 patients with 14 eyes undergoing macula off retinal detachment repair with pars plana vitrectomy, endo-laser and silicone oil-based tamponade compared with 14 fellow healthy eyes at 1, 6 and 12 weeks post-operative period. The study was conducted at the Research Institute of Ophthalmology, Giza, Egypt between February 2018 and August 2018. RESULTS: The foveal avascular zone (FAZ) area in the patients group was not significantly different compared to the control group and was found to be negatively correlated with the central retinal thickness in both the study and control group. The superficial capillary plexus (SCP) area at the FAZ was significantly larger than the deep capillary plexus (DCP) area at the FAZ in both the study and control group over the follow-up period. The DCP area at the FAZ was significantly larger at the 3rd follow-up than the 1st follow-up. The SCP FAZ area was significantly larger than the DCP FAZ area in both the study and control group over the follow-up period. BCVA was found to be negatively correlated to the retinal thickness of the temporal 3 mm paracentral quadrant with no correlation with central foveal thickness (CFT) and the FAZ area. CONCLUSION: Optical coherence tomography (OCT) and OCTA are valuable noninvasive imaging tools to monitor and predict the structural changes at the foveal avascular zone during the recovery phase after successful retinal reattachment involving macula.

Effect of Intraocular Lens Tilt and Decentration on Visual Acuity, Dysphotopsia and Wavefront Aberrations.

Tilt and decentration of intraocular lenses (IOL) may occur secondary to a complicated cataract surgery or following an uneventful phacoemulsification. Although up to 2-3° tilt and a 0.2-0.3 mm decentration are common and clinically unnoticed for any design of IOL, larger extent of tilt and decentration has a negative impact on the optical performance and subsequently, the patients' satisfaction. This negative impact does not affect various types of IOLs equally. In this paper we review the methods of measuring IOL tilt and decentration and focus on the effect of IOL tilt and decentration on visual function, in particular visual acuity, dysphotopsia, and wavefront aberrations. Our review found that the methods to measure the IOL displacement have significantly evolved and the available studies have employed different methods in their measurement, while comparability of these methods is questionable. There has been no universal reference point and axis to measure the IOL displacement between different studies. A remarkably high variety and brands of IOLs are used in various studies and occasionally, opposite results are noticed when two different brands of a same design were compared against another IOL design in two studies. We conclude that <5° of inferotemporal tilt is common in both crystalline lenses and IOLs with a correlation between pre- and postoperative lens tilt. IOL tilt has been noticed more frequently with scleral fixated compared with in-the-bag IOLs. IOL decentration has a greater impact than tilt on reduction of visual acuity. There was no correlation between IOL tilt and decentration and dysphotopsia. The advantages of aspheric IOLs are lost when decentration is >0.5 mm. The effect of IOL displacement on visual function is more pronounced in aberration correcting IOLs compared to spherical and standard non-aberration correcting aspherical IOLs and in multifocal versus monofocal IOLs. Internal coma has been frequently associated with IOL tilt and decentration, and this increases with pupil size. There is no correlation between spherical aberration and IOL tilt or decentration. Although IOL tilt produces significant impact on visual outcome in toric IOLs, these lenses are more sensitive to rotation compared to tilt.

Functional and aesthetic outcomes of eyelid skin grafting in facial nerve palsy.

AIM: To report the functional and aesthetic outcomes of eyelid full-thickness skin grafting (FTSG) in patients with facial nerve palsy (FNP). METHODS: This is a retrospective, non-comparative, single-centre review of all patients with FNP who underwent FTSG over an 8-year period. Functional outcomes were collected through case notes review: CADS (cornea, static asymmetry and dynamic and synkinesis) score facial nerve grading and lagophthalmos on blink, gentle and forced closure. Marginal reflex distance (MRD1 and MRD2) was calculated on standardised photographs. The aesthetic outcomes were assessed objectively by two blinded independent assessors who assessed standardised photographs based on a mutually agreed grading scale. Both functional and aesthetic outcomes were measured preoperatively, and at early (1-3 months), intermediate (3-6 months) and late (>9 months) postoperative periods. RESULTS: A total of 28 eyelid FTSGs were performed on 21 patients (11 female, 10 male) between 2008 and 2016. The mean age was 68 (range, 16-89) years and the mean follow-up was 20.8 (range, 12-30) months. The CADS score (cornea (p<0.001), static asymmetry (p<0.001), dynamic function (p<0.001)), MRD2 (p=0.002) and lagophthalmos (blink (p=0.003), gentle (p<0.001), forced (p=0.003)) improved through early and late postoperative periods. Aesthetically, the grafts appeared to look natural in terms of colour, surface contour and graft edge from the intermediate postoperative period and continued to improve significantly by the late postoperative period. CONCLUSION: The use of periocular FTSG is effective in improving lagophthalmos and periorbital symmetry in patients with FNP where skin contraction exists. They should be considered as an adjunct to other oculoplastic procedures for both functional and aesthetic rehabilitation.

Combined Use of Rituximab and Intravenous Immunoglobulin for Severe Autoimmune Cicatricial Conjunctivitis-An Interventional Case Series.

PURPOSE: Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC. METHODS: In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1-3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosuppressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle-corrected visual acuity <0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging). RESULTS: In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated. CONCLUSIONS: Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further prospective controlled studies on efficacy and safety are warranted before widespread clinical application.

Rapid onset of severe ocular injury after exposure to a button battery.

Button batteries are commonly used in many household electronic items and are a potential health hazard, especially in children. We present the case of a 2-year-old girl presented with swelling and redness of her right eye of 3 hours' duration. Examination revealed a button battery that had became lodged in the superior fornix of her right eye. After the intact battery was removed, the patient was found to have suffered an alkali burn to the underlying conjunctiva and sclera. The burn healed with symblepharon formation.

Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy.

PURPOSE: The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects. METHODS: A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33-0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2-0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37-1.19). CONCLUSIONS: We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan.