This is to certify that this dissertation entitled “STUDY OF THE EFFECT OF GRIDLASERPHOTOCOAGULATION ON CONTRASTSENSITIVITY IN DIABETICMACULARODEMA ” is a bonafide record of the research work done by Dr. RAMYA.M., post graduate in Regional Institute of Ophthalmology Government Ophthalmic Hospital, Madras Medical College and Research Institute, ,Chennai-03, in partial fulfillment of the regulations laid down by The Tamil Nadu Dr.M.G.R. Medical University for the award of M.S. Ophthalmology Branch III, unde r my guidance and supervision during the academic years 2009-2012.
In patients with VA 6/36, 75% cases gained 6/12 or better. In patients with VA 6/60, 60% gained 6/12, There was only 1 case with VA Finger Counting at 1m who improved to 6/18 on D1. The improvement in visual acuity on Day1 was found to be statistically significant (p value= .001) indicating an immediate improvement in visual acuity after this procedure. Visual acuity done on D7of capsulotomy showed that in VA 6/18 group, 90% cases gained 6/12or better. In VA 6/24 group, 84% had VA 6/9 or better. In VA 6/36 group, 50% had VA 6/9 or better. In VA 6/60 group, 90% had 6/12. There was only 1 case with VA FC at 1m who improved to 6/9 on D7. The improvement of visual acuity on day 7 was found to be statistically significant (p value=.000). Visual acuity done at 1 month of capsulotomy showed that in 6/18 group, 92 % gained 6/9 or better vision. In 6/24 group, 88% cases gained 6/9 or better vision. The improvement of visual acuity when compared to pre-laser values was found to be statistically significant (p value=.000). Visual acuity done at 3 months of capsulotomy remained same as at 1 month. This improvement when compared to pre-laser visual acuity was found to be statistically significant (p value=.000).
Our study is important because it used CS change as the primary efficacy endpoint and the results support the use of CS as an independent parameter for determining treatment outcomes in future clinical studies in DME. The data presented here add to the existing knowledge that the evaluation of change in CS provides valuable additional information and should be considered in conjunction with VA measurement when assessing the effect of new treatment modalities. Furthermore, the study design did not include a washout period, which is not typically employed in clinical practice when considering a switch in pharmaceutical agents; therefore, our study closely mimics clinical practice patterns, offering insight into the impact of treatment change in a real-world setting.
In the study we found that around 38% of the eyes treated with laserphotocoagulation had an improvement in BCVA compared to the baseline, while 40% maintained a stable vision. Remaining 23% had a drop in the post laser BCVA in the final follow up. CS improved from the baseline in 49.1% (26 eyes) of the eyes out of which 61.5% (16 eyes) had undergone focal laser for DME. A decrease in CS compared to baseline was observed in 20% of the eyes undergoing PRP which is more as compared to that with focal laser (9%). Lövestam-Adrian et al. 15 in their study in 20 eyes treated with PRP for proliferative diabetic retinopathy too noted a loss in CS following PRP compared to the untreated eyes. Despite of the fact that focal laser has its maximum effect on the cones at macula, CS improves the most after focal laser due to the resolution of macular edema following treatment.
ing the relatively short follow-up period of this study, it should be mentioned that a higher rate of cataract progression might be observed in the IVTA group upon longer-term follow-up of patients. Some limitations of our study are inherent, and include possible confounding influence of cataract progression on VA scores in the IVTA group, our small sample size, limited duration of follow-up, and a lack of proper control group. We observed a significant increase in average cataract grading in the IVTA group, and the mean VA effect in the IVTA group might be underestimated because of lens opacification that was not considered to be of sufficient clinical significance to merit surgery at the time of observation. Since the modified gridlaser treatment has been a standard care for diffuse DME and the gridlaserphotocoagulation combined with IVTA has also shown promising results, 37 a
significantly increased the contrastsensitivity at low and medium spatial frequencies . Furthermore, a signifi- cant improvement in the vision-related quality of life was reported. Recently, the Central Retinal Enrichment Supplementation Trial (CREST) study reported a signifi- cant increase in contrastsensitivity of subjects free of retinal disease after the daily consumption of the same formulation used in the previous studies compared to placebo . In our study, two years after the daily supplementation with Macushield in patients with type 2 diabetes, mfERG macular responses signifi- cantly improved and foveal thickness increased com- pared to baseline findings, indicating an improvement of visual function. Visual acuity did not change over the study period, which is consistent with the CREST study as well as with the studies concerning patients with early AMD [13, 29].
Patients in the observation group received an intravitreal injection 1 week before photocoagulation in the operating room. Patients were first narcotized with alcaine, followed by disinfection and draping. A needle was inserted into the area 3.5 mm behind the corneoscleral limbus below the temple and was perpendicular to the sclerotic surface. Next, 10 g/L ranibizumab was slowly injected into the vitreous body. Gentle pressure was applied to the injection spot with an aseptic cotton bud for 1–2 minutes after medicine injec- tion to prevent backflow. The operative eye was smeared with ofloxacin eye ointment and bound. The patients were reexamined 1 month after receiving laserphotocoagulation. Those whose measurements showed no decrease in the central macular thickness (CMT) of the fovea were injected with ranibizumab (10 g/L) again. The interval between the two injections was 1 month.
Previous studies from other countries have similar findings regarding a significant reduction in CMT and BCVA improvement following the use of intravitreal bevacizumab injections for ME secondary to RVO [12-14]. Abegg et al.  reported that visual acuity was significantly better 4 to 6 weeks after bevacizumab treatment and the gain in visual acuity was accompanied by a significant decrease in retinal thickness from 454±117 µm to 305±129 µm. In another study, Gutiérrez et al.  reported that the mean BCVA improved from 1.32±0.24 logMAR at baseline to 0.8±0.15 logMAR (p=0.0003) at the 6-month follow-up and the CMT improved from 615±116 µm to 420±72 µm. Manayath et al.  present similar successful results in 2009.
Dilated fundoscopy with slit lamp biomicroscopy and 78 D lens was performed by a specialist registrar (RW) to con- firm the grading of CSMO according to the Early Treat- ment Diabetic Retinopathy Study extension of the modified Airlie House classification . CSMO is defined as any retinal thickening within 500 microns of the centre of the fovea; hard, yellow exudates within 500 microns of the centre of the fovea with adjacent retinal thickening; or at least 1 disc area of retinal thickening, any part of which is within 1 disc are of the centre of the fovea. Each age group (eg. 30–49 years old, 50–69, 70–89) sep- arated by 2 decades was assigned pass-fail criterion for TCCT as previous data suggests age related change in threshold for tritan colour. Since this is the first study of NPDR using the Chromatest, threshold levels were derived using the same data set for both training and test-
Background: This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laserphotocoagulation in patients with diabeticmacular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment. Methods: An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laserphotocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with ≥ 10 and ≥ 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network). Results: Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90 – 8.52 ETDRS letters), ≥ 15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12 – 4.20), and ≥ 10 ETDRS letter loss (OR 0.25, 95% CrI 0.05 – 0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26 – 10.61 ETDRS letters) (IPD and aggregate random-effects model).
Totally 202 babies were screened in a duration of two years. The mean gestational age of babies screened was 30.25 weeks and the mean birth weight was 1.25 Kg. out of the 202 babies screened, 73 babies had ROP. Three pairs of twins were also affected by ROP among others. Out of the 73 ROP babies 17 required laser treatment. 14 of those who were treated with laser recovered whereas 3 babies progressed to retinal detachment, most probably due to late stage of presentation. The probability value was found to be 0.008 which is significant.
Limitations of the current study are the retrospective nature and small sample size. Our study lacked control arms: patients who were continued on IVB alone when their macular edema recurred, and those who received continuous monthly IVB throughout the study period. In addition, this study consisted of only those patients with recurrent macular edema, so that it is difficult to compare our current results with those of other reports. Based on the current results, however, the effect of this combination therapy on visual recovery is limited. Because the total number of injections of IVB was 2.8 ± 0.7 for both the BRVO and CRVO groups during a mean total follow-up period of 29.3 ± 5.8 months, the number of IVB injections is low. In addition, gridphotocoagulation in our study was performed quite safely and with low laser intensity. Based on the current results, we suggest that grid photocoagula- tion combined with IVB be used for recurrent macular edema associated with RVO – at least when it is difficult to perform repeated IVB.
and HbA1c levels have a positive correlation to the onset and progression of DR. VEGF, a mito- gen for endothelial cells, is a key angiogenic factor for stimulating new vessel formation and vascular hyper-permeability in DR, and due to its expression both in-vivo and in-vitro can be induced by retinal hypoxia . DR results in a series of changes, including increased retinal vascular permeability, chronic retinal hypoxia and extensive retinal ischemia; the processes of which are thought to be mediated by vari- ous growth factors such as VEGF . HbA1c is regarded as a biochemical model for the patho- genesis of DR through glycosylation reactions . The metabolic control, reflected by blood glucose level and HbA1c value, accounts for an important factor for the onset and progression of DR, making HbA1c varying with DR progres- sion . Early epidemiologic studies show a critical relationship between HbA1c levels and the incidence of DR, making it feasible to avoid progression of DR with tight glycemic control . Cavusoglu et al.  argue that progres- sively increasing VEGF serum and HbA1c le- vels bear a correlation with the degree of DR, which is in agreement with our results. The- refore, VEGF serum and HbA1c levels are asso- ciated with the severity of DR in patients. The same study also argues that VEGF serum and HbA1c levels are down-regulated after laserphotocoagulation in DR patients, and that VEGF serum and HbA1c levels in the NPDR group were significantly lower when compared to the PDR group. Laserphotocoagulation, in which laser burns are placed over the entire retina except the central macula, is an estab- lished technique for treating severe DR . It promotes regression and arrests progression of retinal neovascularisation while ameliorating retinal ischemia and hypoxia, thus inhibiting VEGF activity and causing a reduction in isch- emia-driven VEGF production, which eventually causes VEGF serum levels to decrease . The same result was observed by Lip et al. in their pilot study, where they suggest that the angiogenic stimuli responsible for increased VEGF appeared to decrease during laser photo- coagulation . Qiao et al. found that laser pho- tocoagulation can reduce VEGF serum and HbA1c levels , which is in agreement with our studies. In addition, it was found that the lower the VEGF and HbA1c levels were, the bet- ter the visual acuity recovery and therapeutic
necrosis in the majority of cases. It is difficult, again, to be certain that the ultrasound measurements and the pathology measurements were taken in the same plane. However, it is likely that the area of laser induced necrosis around the fibre tip is roughly spherical, so the diameter of necrosis will be approximately the same in all planes. The changes seen on ultrasound during ILP represent bubble formation in the tissues(from vapourization of tissue water) which disappear after the laser is switched off and coagulation and charring(changes which persist after cessation of the treatment) which probably do not extend to the full limits of the necrosed area. In experimental work Malone et al(1992) have also found ultrasound to be inaccurate in assessing the final extent of ILP induced necrosis whereas Dachman et al(1990), Bosman et al(1991) and Steger et al(1992)all found good correlation between ultrasound images and histology. It should be stressed that all these studies were performed in normal liver rather than in tumour tissue. The clinical work described by Amin et al(1993) used ultrasound to place the needles(and fibres) and to monitor ILP of hepatic métastasés and found little correlation between the hyperechoic areas seen on ultrasound during ILP and the devascularised areas visible on dynamic CT scans 24 hours post ILP although correlation between images and histology was not possible as the tumours were not resected and no post mortems were performed. The hyperechoic areas were always visible at ultrasound during ILP of hepatic métastasés and were often impressive in size but in some of our patients little in the way of hyperechoic areas were visible during ILP. Again, as mentioned above ultrasound is particularly operator dependent which may influence the results and explain the differences reported. It was however useful in placing the needle in the tumour although another imaging technique is needed to match the image with the extent of thermal necrosis seen microscopically. From the diagnostic point of view, colour doppler has shown promise(Cosgrove et al, 1993, McNicholas, M. et al, 1993) in predicting whether breast tumours are benign or malignant but has yet to be assessed in the imaging of laser tissue interactions.
DIAMONDS STUDY GROUP: Noemi Lois, Queen ’ s University and Royal Victoria Hospital, Belfast H&SC Trust; Evie Gardner, NICTU, Belfast; Norman Waugh, Warwick University, Warwick; Augusto Azuara-Blanco, Queen ’ s University and Royal Victoria Hospital, Belfast H&SC Trust, Belfast; Hema Mistry, Warwick University, Warwick; Danny McAuley, Queen ’ s University and Royal Victoria Hospital, Belfast H&SC Trust, Belfast; Mike Clarke, Queens University, Belfast; Tariq M Aslam, Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester; Clare Bailey and Tomas Burke, Bristol Eye Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol; Victor Chong, Royal Free Hospital NHS Foundation Trust, London; Sobha Sivaprasad, Moorfields Eye Hospital NHS Foundation Trust, London; David H Steel, Sunderland Eye Infirmary, City Hospitals Sunderland NHS Foundation Trust, Sunderland and Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, Newcastle; James Stephen Talks, Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle; Catherine Adams, NICTU, Belfast; Christina Campbell, NICTU, Belfast; Matthew Mills, NICTU, Belfast; Paul Doherty, NICTU, Belfast; Aby Joseph, NICTU, Belfast; Nachiketa Acharya, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield; Seema Arora, Hull and East Yorkshire Hospital, Hull and East Yorkshire NHS Trust; Harbhajan Kaur Arora, Frimley Park Hospital NHS Foundation Trust; Mandeep S Bindra, Stoke Mandeville Hospital, Buckinghamshire NHS Trust; Farahat Butt, Bradford Teaching Hospitals NHS Trust, Bradford; Manju Chandran, Frimley Park Hospital NHS Foundation Trust; Richard Cheong-Leen, Hillingdon Hospitals NHS Foundation Trust; Mark Costen, Hull and East Yorkshire Hospital, Hull and East Yorkshire NHS Trust; Bhatia Devangna, Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle; Louise Downey, Hull and East Yorkshire Hospital, Hull and East Yorkshire NHS Trust; Stefanos Efraimidis and Haralabos Eleftheriadis, Kings College Hospital
This is a study of existing data on 67 eyes from 54 pa tients with Eales' disease, referred to the Labbafinejad Medi cal Center (LMC) from 1988 to 1998. Our main outcome measure was visual acuity changes of treated patients. Vi sual acuity of patients had been checked before and after procedures, and during follow ups. Every patient had a thor ough recorded history and physical examination including: slitlamp examination, checked lOP with applanation tonom eter, and complete fundus examination by indirect ophthal moscope with scleral depression and three mirror lens.
Inclusion criteria included ability to provide writ- ten informed consent, age 18 years or older, adequately clear media for SD-OCT imaging, and Snellen visual acuity of 20/40 to 20/300 in the study eye. Anatomic cri- teria for inclusion required CRT ≥ 350 μm on SD-OCT and recalcitrant DME was defined as persistent cystic change with ≤15% decrease in CRT over the 6 months prior to IAI switch despite having at least 4 total treat- ments for DME, with at least 3 of these treatments being intravitreal anti-VEGF injections (excluding IAI). Treat- ments for DME prior to IAI switch included intravitreal bevacizumab (IVB) and ranibizumab (IVR), intravitreal triamcinolone acetonide (IVTA), sub-Tenon’s triamci- nolone acetonide (STTA), dexamethasone intravitreal implant (Ozurdex; Allergan, Irvine, California), and laserphotocoagulation. If both eyes of a patient met entry criteria, then the worse-seeing eye was included in the study. If patients were treated with previous cor- ticosteroids, baseline intraocular pressure had to be 21 mm Hg or less either with or without pressure reduc- ing drops. Those patients who were previously treated with corticosteroids also had to have adequate clar- ity of media to allow adequate SD-OCT image quality. Patients were excluded if they had previously received intravitreal aflibercept in the study eye or a history of systemic anti-VEGF therapy. Inclusion and exclusion criteria are outlined in Table 1.
Luttrull et al. showed increased burn risk for 810 nm subthreshold laser with more than 5%DC.  This risk in- creases with decreasing wavelength, which may have been the reason for visible burn in one out 10 eyes with 15%DC. This needs further clarification in terms of safety with lar- ger sample size including 5%DC group. However, this study supports the safety of subthreshold laser over the CW laser. Limitations of our study include small sample size in each group and short follow up. Our study did not sci- entifically analyze microaneurysm closure rate. However, this is the first study, which compares effect of different duty cycle subthreshold dosage with standard ETDRS laser dosage in diabeticmacular edema. However, less number of subthreshold laser applications over a limited area of DME may be the reason for suboptimal response. Due to ethical issues, we did not include center-involving edema, which may have responded differently due to more severity and further loss of retinal sensitivity, and may have influenced the outcome measures.
The pilot prospective study received approval by the institutional review board of Rafik Hariri University Hospital and followed the tenets of the Declaration of Helsinki. The study was carried out from January 2015 to December 2018. Consecutive patients with naïve DME underwent spectral domain optical coherence tomography (OCT) and fluorescein angiography (FA) of the midperiphery and were offered to have continuous injections of anti-VEGF agents (treat and extend) if they were compliant, or PPRP with modified (flexible) pro re nata (PRN) injections if they felt unable to be followed frequently (bodily handicap; living abroad; long-distance travel; frequent hospitalizations; phobia of injections; and poor financial resources). The patient consent was both written and informed consent.
reported the bene ﬁ t of IVB as an additive treatment to PRP in reducing DME and ME secondary to PRP. 20 In the present study, eyes in group A received IVB injection 1 week prior to the ﬁ rst session of PRP, while eyes in group B received IVB injection 1 week after the last session of PRP. CMT was evaluated before and 1 month after injec- tion. CMT reduction of eyes in group A was consistent with previous studies. 21 Bevacizumab prevented ME sec- ondary to PRP in these patients. However, eyes in group B also had decreased CMT. There was no signi ﬁ cant differ- ence in the change of macular thickness between groups. Reduction of VEGF activity was still able to catch up to PRP, stabilizing secondary ME. The visual acuity pre- and post-treatment between the two groups were signi ﬁ cantly signi ﬁ cant; however, these ﬁ ndings were suggested due to the different staging and severity of the DR.