Mazhar Ishaq

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR).

Determining the efficacy of corneal crosslinking in progressive keratoconus.

Objective: To determine the Efficacy of Corneal Crosslinkage (CXL), using Corneal Topography, in eyes with progressive Keratoconus. Methods: This randomized control trial was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from October 2013 to April 2014. A total of 60 eyes of 30 patients were included who presented with bilateral progressive Keratoconus. Each eye of the patient was randomized either to a treatment group (Group-A) or control untreated group (Group-B) of 30 eyes each. A written informed consent was obtained from each patient, following which corneal crosslinkage (CXL) with topical riboflavin eye drops was performed. Follow up visit was done at three months post operatively, Corneal topography was repeated and recorded. Results: The mean age of the patients was 23.13±7.62 years (range 13 to 39 years). There were 26 males and 34 females patients. The mean simK value at the start of study was 50.94±4.84 diopters in Group-A and 49.73±5.24 diopters in Group-B. At three months follow-up, the mean simK value was significantly lower in Group-A (48.28±4.47) as compared to Group-B (51.11±4.85). Keratoconus improved/ remained stable in 34 (56.7%) eyes while progressive disease was noted in 26 (43.3%) eyes. When compared between the groups, the frequency of efficacy was significantly higher in Group-A (86.7% vs. 26.7%; p=.000) as compared to Group-B. Conclusion: Corneal Crosslinking was found effective in causing regression or halting the progression of disease in patients with progressive Keratoconus at three months follow-up, however, the efficacy of corneal crosslinking was unaffected by patient’s age and gender.

Efficacy of intravitreal bevacizumab combined with pan retinal photocoagulation versus panretinal photocoagulation alone in treatment of proliferative diabetic retinopathy

Objective: To compare effectiveness of pan-retinal photocoagulation alone versus panretinal photocoagulation combined with intravitreal bevacizumab on visual acuity and central macular thickness in patients presenting with proliferative diabetic retinopathy. Methods: This Randomized controlled trial was carried out at Armed Forces Institute of ophthalmology, Pakistan from Jan 2016 to Aug 2016. Seventy six eyes of 50 patients having proliferative diabetic retinopathy and diabetic macular edema were included in the study. All the patients were subjected to detailed clinical examination that included Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), slit lamp examination of anterior and posterior segments. Optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) were carried out and patients were divided in two groups (GP and GI). Three monthly sessions of Pan retinal photocoagulation (PRP) using Pattern Scan Laser (PASCAL) alone was performed in group GP while PRP along with three monthly intravitreal bevacizumab (IVB) was performed in group GI. BCVA and CMT was recorded 04 weeks after the third PRP session in both the groups. Results: Seventy six eyes of 50 patients (38 in each group) were treated with three sessions of PRP alone and PRP with IVB in Group GP and GI respectively. Mean age of the patient in group GP was 57.47± 6.08 years while that in group GI was 55.69 ±6.58. The magnitude of induced change in BCVA was 0.09 ± 0.15 in GP while 0.22 + 0.04 in GI groups while mean induced change in CMT after treatment was 77.44 ± 92.30 um and 117.50 ± 93.82 um in group GP and GI. Conclusion: Laser PRP combined with IVB has superior visual and anatomical outcome than PRP alone in patients with combined presentation of PDR and DME.

Effect of wavefront optimized LASIK on higher order aberrations in myopic patients.

Objective: To determine mean change induced in root mean square value of higher order aberrations in myopic patients undergoing wavefront optimized laser assisted in situ keratomileusis. Methods: This quasi experimental study was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from Jan 2014 to Dec 2014. Sixty eyes of 35 myopic patients were included in the study. All patients underwent wavefront optimized (WFO) laser assisted in situ keratomileusis (LASIK) using femtosecond laser (FM 200Wavelight technologies) and excimer laser (Ew 500Wavelight technologies). Higher order aberrations (HOAs) were measured with aberrometer (Wavelight allegro analyzer version 1073) during preoperative assessment and one month after surgery. Results: All 35 patients ranged from 20 to 32 years with a mean age of 24 ± 3.41 years. Refractive error ranged from -1.00 to -9.50 DS with a mean spherical equivalent (SE) of -3.73 ± 1.95 before surgery and - 0.36 ± 1.50DS one month after LASIK. Uncorrected visual acuity (UCVA) was improved to 0.00 or better in all 60 eyes. An increase of 1.56 fold was observed in RMS of total HOAs. Among the HOAs, a statistically significant positive correlation was observed between spherical aberrations (4th order aberration) and preoperative spherical equivalent. Conclusion: In spite of excellent improvement in refractive error, significant amount of higher order aberrations were induced after WFO LASIK.

Comparison of higher order aberrations in patients with various refractive errors.

Objective: To compare the mean root mean square (RMS) of total higher order aberrations (HOAs), coma and spherical aberrations in individuals with myopia, hypermetropia and myopic astigmatism. Methods: This prospective analytical study was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from Jan 2014 to Dec 2014. Two hundred eyes of 121 patients with age ranging from 18-40 years were included in the study. Patients were divided into 4 group namely Low myopia, High myopia, Astigmatism and Hypermetropia on the basis of refractive error. Included were the patients who had refractive error more than ± 0.5D and best corrected visual acuity (BCVA) of 0.00 or better. Patients who had history of surgery and / or eye disease were excluded from the study. Visual acuity (VA), Spherical equivalent (SE) of refractive error, RMS value of total HOAs, coma and spherical aberrations were evaluated. HOAs were measured with aberrometer (Wavelight analyzer version 1073) at 6 mm pupil size. Results: Age of the patients ranged from 18 years to 40 years with mean age of 29.10±10.6 years. Seventy one (35.5%) were males and 129 (64.5%) were female. Mean RMS value of HOAs, coma and spherical aberrations was calculated in all four groups. RMS of total HOAs and spherical aberrations in hypermetropia was 0.96±0.96 and 0.30±0.42 respectively and it was higher than other three groups. Conclusions: In overall comparison the mean RMS of total HOAs and spherical aberrations was significantly increased in hypermetropia group and there was a statistically significant negative correlation of SE of hypermetropia with RMS of total HOAs and spherical aberration.

TNF-α Genetic Predisposition and Higher Expression of Inflammatory Pathway Components in Keratoconus

Purpose To date keratoconus (KC) pathogenesis is undefined; however, the involvement of inflammatory pathways in disease development is becoming apparent. In the present study, we investigated the role of a promoter region polymorphism rs1800629 (-308G>A) in the inflammatory pathway component TNF-α and its effects on the expression of TNF-α and downstream molecules tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and interleukin 6 (IL-6) in KC development. Methods TNF-α promoter polymorphism rs1800629 (-308G>A), was genotyped in 257 sporadic KC patients and 253 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was performed to assess for the -308G>A genotypes. Quantitative polymerase chain reaction (qPCR) was carried out to compare the mRNA expression of TNF-α, TNFR1, TNFR2, RELA, and IL6 in the corneal tissues of 20 KC patients and 20 donor controls. Results The -308G>A genotype GA was found to be significantly associated with KC development (dominant model [odds ratio (OR) = 6.67 (95% confidence interval [CI] = 4.28-10.42), P < 0.001]) and allele-A (OR = 4.30, 95%CI = 2.93-6.34, P < 0.001). TNF-α serum levels were significantly raised in patients with GA genotype (196.5 ± 69.5 pg/mL) compared to reference genotype GG (21.7 ± 8.2 pg/mL) (P < 0.0001). There was a significant overexpression of TNF-α (P = 0.002), TNFR2 (P = 0.0001), RELA (P = 0.0117), and IL6 (P = 0.0007) in the KC corneal tissues as compared to the control. Conclusions The GA genotype of the TNF-α -308G>A polymorphism is a significant genetic risk factor for the pathogenesis of KC. Moreover, this single nucleotide polymorphism (SNP) was observed to be associated with deregulated expression of downstream molecules, thus further reinforcing the role of the inflammatory pathway components in the development of KC.

Effect of pan retinal photocoagulation on central macular thickness and visual acuity in proliferative diabetic retinopathy.

Objective: To evaluate the effect of pan-retinal photocoagulation with Pattern Scan Laser (pascal)on best corrected visual acuity and central macular thickness in patients having proliferative diabetic retinopathy (PDR). Methods: This study was conducted at AFIO, Rawalpindi, Pakistan from Oct 2014 to Jul 2015. Sixty seven eyes of 46 patients having proliferative diabetic retinopathy were included in the study. All patients underwent ophthalmic clinical examination including uncorrected distant visual acuity (UCVA), best corrected visual acuity (BCVA), fundus examination with slit lamp and optical coherence tomography to document the pretreatment central macular thickness (CMT). Two sessions of PRP using Pattern Scan Laser were performed 04 weeks apart and OCT was repeated 04 weeks after the 2nd session. Central macular thickness and BCVA were documented. Results: Sixty seven eyes of 46 patients (29 females and 17 males) with mean age of 57.45 ± 5.78 years underwent treatment with two sessions of laser PRP. Mean pretreatment BCVA was 0.67 ± 0.43 and mean post-treatment BCVA was 0.57 ± 0.3. Mean central macular thickness (CMT)as measured by OCT was 391.93 ± 170.43 before treatment and 316.91 ± 90.42 um after treatment. The magnitude of induced change in CMT after treatment was 75.01 ± 90.75 and BCVA was 0.09 ± 0.14. Conclusion: Laser PRP with Pattern scan laser alone in patients with combined presentation of PDR and DME is safe and effective.

Agreement between Keratometric readings by VERION image guided System, Galilei G4 and Pentacam

Objective: To study Agreement between Keratometric readings by VERION image guided System, Galilei G4 and Pentacam. Methods: The quasi experimental study was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from August 2016 to December 2016. Twenty five patients fulfilling the inclusion criteria participated in the study. All Patients were subjected to Keratometric assessment using Galilei G4 Dual Scheimpflug analyzer (Ziemer, Switzerland), Wavelight Oculyzer II (Pentacam, Germany) and Verion image guided system (Alcon). Steep and flat meridian and diopter of astigmatism by three systems were recorded and endorsed. All readings were taken by the same observer. Statistical Program for Social Sciences (SPSS) version 22.0 was used for statistical analysis. Results analyzed for significance by t-tests and Interclass correlation analysis. In t tests, P values of <0.05 was considered statistically significant while interclass coefficient of >0.7 was considered acceptable. Results: Fifty eyes of twenty-five patients (22 male, 28 female) with mean age of 29.50 ± 3.46 years were studied. Flat K, steep K and dioptric power of astigmatism were measured with verion, pentacam and Galilei G4. Interclass correlation analysis showed agreement between individual variables measured by the three devices, while one sample t test showed no significant difference between dioptric power of astigmatism between Verion-Pentacam and Verion- Galilei group. (p 0.178 for former and 0.622 for later group). Conclusion: Verion image guided system is comparable to other instruments used currently for keratometry. Verion can be interchangeably used with Pentacam and Galilee G4 in assessing corneal astigmatism.

Comparison of transepithelial corneal crosslinking with epithelium-off crosslinking (epithelium-off CXL) in adult Pakistani population with progressive keratoconus

PURPOSE: The purpose of this study is to compare the safety and efficacy of transepithelial corneal crosslinking (CXL) with epithelium-off crosslinking (epithelium-off CXL) in the treatment of progressive keratoconus in adult Pakistani population. MATERIALS AND METHODS: Sixty-four eyes of 64 consecutive patients of progressive keratoconus were included in this quasi-experimental study. Thirty-two eyes received transepithelial CXL with Peschke TE (0.25% riboflavin (Vitamin B2), 1.2% hydroxypropyl methylcellulose (HPMC), 0.01% benzalkonium chloride) and 32 eyes received epithelium-off CXL with Peschke M (0.1% riboflavin (Vitamin B2) 0.1%, HPMC 1.1%.) The cornea was then exposed to ultraviolet A light at an irradiance of 3 mW/cm2 for 30 min. The primary outcome measure, clinical stabilization of keratoconus was defined as an increase of no more than 1D in Kmaxat 1 year. Other parameters evaluated at baseline and 3, 6, 12, and 18 months postoperatively were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE), astigmatism (Ast), simulated keratometry, steep keratmetry (steep K), and corneal thickness at thinnest point (pachy thin). RESULTS: Both epithelium-off CXL and transepithelial CXL groups showed a significant reduction in Kmax, steep K, simulated K, corneal pachymetry at all test points (P < 0.05) with significantly greater reductions achieved in epithelium-off CXL group at 18 months follow-up. The mean UDVA, CDVA, SE, Ast significantly improved in both groups (P < 0.05). The mean postoperative UDVA and CDVA between the groups were not significant at 12 months (P = 0.650, 0.018, respectively). Clinical stabilization was achieved in 94% of eyes in epithelium-off CXL and 75% of eyes in transepithelial CXL. In epithelium-off CXL, three eyes exhibited stromal haze resolved by corticosteroid treatment. No complication was documented in transepithelial CXL group. CONCLUSION: Transepithelial CXL is not recommended to be replaced completely by standard epithelium-off CXL due to continued ectatic progression in 25% of cases. However, thin corneas, unfit for standard epithelium-off CXL, can benefit from transepithelial CXL.

Change in central corneal thickness, corneal endothelial cell density, anterior chamber depth and axial length after repair of rhegmatogenous retinal detachment

Objective: To compare the effects of Pars Plana Vitrectomy (PPV) and Scleral Buckling (SB) with reference to Central Corneal Thickness (CCT), Corneal Endothelial-Cell Density (CED), Anterior Chamber Depth (ACD) and Axial Length (AL) in repair of Rhegmatogenous Retinal Detachment (RRD). Methods: This comparative cross sectional analytical study was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from July 2013 to July 2015. A total of 69 eyes of 69 patients which underwent repair of RRD by either PPV or SB were analyzed to compare mean change in CCT, CED, ACD and AL between two groups. Results: Mean age of patients was 56.23±5.22 years. Mean pre-operative CCT, CED, ACD and AL in PPV group was 533.06±13.28µm, 2231.67±164.57Cells/mm2, 3.37±0.18mm and 23.66±0.76mm respectively. Mean post-operative CCT, CED, ACD and AL in PPV group was 534.81±11.83µm, 2037.19±167.83 Cells/mm2, 3.24±0.13mm and 23.88±0.80mm respectively. Change in CED, ACD and AL from pre-operative value after PPV was statistically significant (p<0.001). Mean pre-operative CCT, CED, ACD and AL in SB group was 530.73±12.59 µm, 2161.79±161.96 Cells/mm2, 3.343±0.14mm and 23.67±0.82mm respectively. Mean post-operative CCT, CED, ACD and AL in SB group was 532.76±7.74 µm, 2158.27±156.58 Cells/mm2, 3.24±0.10mmand 25.71±0.86mm respectively. Change in ACD and AL from pre-operative value after SB was statistically significant (p<0.001). Mean change of CED, ACD and AL between two groups was also statistically significant (p<0.001). Conclusion: Rhegmatogenous retinal detachment repair causes ocular changes, with significantly more decrease in corneal endothelial cell density after pars plana vitrectomy, and more increase in anterior chamber depth and axial length after scleral buckling.