Progression of Diabetic Retinopathy following uncomplicated phaco-emulsification, a prospective study.

INTRODUCTION

India is regarded as ‘thediabetic capital of the world’. According to International Diabetic Federation,prevalence of diabetes is estimated to be 69.1 million in India in 2015.Theburden of diabetes is increasing year by year and it is projected to increaseto approximately 79.4 million individuals by 20301. Diabetesmellitus causes micro vascular complications due to micro angiopathy, but arenot necessarily directly linked to the level of hyperglycemia. Diabetes affectsthe eye in various forms. Cataract is frequently associated with diabetes alongwith glaucoma and diabetic retinopathy2.

Diabetes and cataract

Asthe incidence and progression of cataract is elevated in patients with diabetesmellitus, cataract is considered as the major cause of visual impairment indiabetics3. Patients with diabetes tend to develop cataract at ayounger age compared to that of non-diabetics.

Hyperglycemia will be reflectedas high level of glucose in aqueous humor, which diffuses into the lens.Normally the hexokinase pathway is used for the metabolism in the lens. But ifblood glucose level exceeds 200mg%, the hexokinase gets saturated and aldosereductase convert the glucose into sorbitol4. Sorbitol ismetabolized slowly by the lens. So, it gets accumulated in the lens cytoplasm. .Osmotic pressure inside the lens slowly increases, causing influx of water andswelling of lens fibres and this ultimately leads to the formation of lensopacities5, 6.

Further studies revealed thatosmotic stress in the lens produced by the sorbitol accumulation causesinduction of apoptosis in the lens epithelial cells, which finally results inthe development of cataract7. Also, hyperglycemia puts the antioxidantpathways into stress and along with the glycosylation of proteins, whichresults in abnormal cross linkage and aggregation, producing cataract8.

Diabetic retinopathy

Diabetic retinopathy is afrequent complication of  both type1 andtype 2 diabetes and is one of the main causes of visual disability in patientswith diabetes9. After 20 years of the disease, 95% of type 1patients and 60% of type2 patients will show signs of retinopathy5. Therisk of developing diabetic retinopathy is according to the type and durationof diabetes, blood pressure and the level of glucose and lipids in the blood10.Diabeticretinopathy is a microangiopathy of the retina which first presents with theappearance of retinal micro aneurysms preferentially at the posterior pole ofthe retina11. It is believed that exposure to hyperglycemia over anextended period result in a number of biochemical and physiologic changes thatultimately cause endothelial damage. Specific retinal capillary changes includeselective loss of pericytes and basement membrane thickening, which favor capillaryocclusion and retinal non perfusion, as well as decompensation of the endothelialbarrier function, which allows serum leakage and retinal edema to occur.

Diabetic retinopathy is classified into NPDR (Non Proliferative Diabetic Retinopathy)which is the background retinopathy and PDR (Proliferative DiabeticRetinopathy) which presents with neovascularization due to retinal ischemia.

Diabeticmacular edema is an important manifestation of diabetes causing visualimpairment. Diabetic retinopathy patients elevated VEGF levels in vitreous andretina ,which causes breakdown of blood – retinal barrier leading to theaccumulation of fluid in the macula12.

Diabeticretinopathy and cataract surgery

Because of the high correlationbetween the duration of diabetes and its complications13, olderpatients who are more likely to have cataract may also have diabeticretinopathy or macular edema. Earlier cataract surgery is important as the lensopacities may preclude the fundus details5. But, usually diabeticcataract extraction has been associated with higher post-operativecomplications than non-diabetics which include progression of diabeticretinopathy, worsening of macular edema, anterior segment neovascularization,posterior capsular thickening and fibrinous uveitis14-16 whichresult in poor visual acuity post operatively.

The progression of diabeticretinopathy and macular edema worsening are considered to be due to breakdownof blood retinal barrier or due to the inflammatory mediators released aftersurgical trauma17. Compared to ICCE and ECCE, phacoemulsification issuggested to be safer to perform in diabetics as it is associated with lesserpost-operative inflammation18. Thus a study on progression ofdiabetic retinopathy following uncomplicated phacoemulsification standsrelevant.

REVIEW OF LITERATURE

Cataractsurgery in diabetic retinopathy patients is a common scenario forophthalmologists to manage now-a-days. Definitive treatments of both theconditions are essential for a better visual prognosis for the patient.Diabetic retinopathy often results in poor visual acuity following cataractsurgery than in patients without retinopathy. Earlier in the 90s, Jaffe23and Schatz et al. 27found out that retinopathy progression is morein the operated eye compared with the fellow control eye. In a follow up study of 21 patients with symmetric NPDRwho underwent ECCE and IOL for 18+/- 7 months by Jaffe et al.23todetermine the incidence and factors predictive of progression of diabeticretinopathy and the final visual acuity, 74% had progression of retinopathy. In37% it progressed only in the operated eye whereas, no patients had progressionin the fellow eye alone. In Schatz et al. study, twenty-three (72%) of the 32 study patients hadasymmetric retinopathy (with the more severe retinopathy in the eye thatunderwent cataract surgery in each case) compared with three (9%) of thecontrol group (P < .0005).the visual acuity results were poorer in eyesundergone cataract surgery with no eye achieving 20/20 or 20/2, only 3 eyesachieved 20/30 or 20/40.

Worseningmacular oedema, continuing anterior and posterior segment proliferation,posterior capsule opacification, or unrelated events, such as retinal vein occlusionmay be the cause of worsening of visual results. Posterior capsularopacification also found to be more in diabetics with retinopathy than in non-diabetics.

Kwon SI 22 and colleagues conducted aretrospective study on macular thickness changesafter cataract surgery in 104 diabetic patients in Korea, using opticalcoherence tomography (OCT) done at 1week, 2 weeks and 6 weeks after thesurgery. Study revealed that 18% patients had macular edema after cataractsurgery, which had a peak incidence of 1 month post-surgery. They concludedthat prior laser treatment might prevent post-operative macular edema until 2months after cataract surgery in diabetic patients.

Various factors have been put forwarded as thecause of worsening of retinopathy. A study was conducted by Henricsson et al.21in the department of ophthalmology in Helsingborg, UK including 70 patientswith 35 mono ocularly and 35 binocularly operated on ( ECCE, SICS, phaco)followed up for 32 months, revealed the importance of good glycemic control inpreventing the progression of retinopathy. Patients in this study includingthose with PDR obtained good visual acuity, better than in most of the previousstudies. Mean level of HbAlC (p=0.04), duration of diabetes(p=0.02), insulin treatment (p=0.001), and presence of retinopathy at baseline(p=0.01) were the factors associated with the progression of retinopathy, whichoccurred in 30 among the 70 operated eyes.

Benson et al.25 found that age wasan important predictor of poor visual outcome. Patients aged 63 or less weremore likely to achieve increase in visual acuity after cataract surgery. Poorerresults in older patients were due to worsening of macular edema.

Various studies compared different surgicaltechniques of cataract in terms of post-operative results. A prospective studydone by Dowler et al.26 with 46 patients having diabetes andbilateral cataract to compare phacoemulsification with ECCE, revealed thatphacoemulsification is associated with better post-operative visual acuity,less post-operative inflammation and less need for capsulotomy. But, there wasno difference in incidence of post-operative CSME or progression of retinopathyor development of high risk retinopathy was identified between the twotechniques.

Borrillo et al.24 have done aretrospective review of 150 eyes of 119 diabetic patients who underwentphacoemulsification over 5 year period and the visual results and rate ofprogression of diabetic retinopathy after phacoemulsification were not muchdifferent from those reported using other techniques. The study proposed thatpre-operative NPDR, prolonged surgical duration and limited surgical experiencewere statistically associated with retinopathy progression.

Ina retrospective study conducted by Shuh-Bin Liao and colleague to analyze theprogression of diabetic retinopathy following uncomplicated phacoemulsification with 3 years follow up, which included 37 diabetic patients withbinocular surgery done in 14 patients and monocular surgery done in 23 revealedthat patients who had mild to moderate NPDR pre-operatively had significantlygreater progression of retinopathy post operatively compared to those withoutpre- operative NPDR. But, they couldn’t find any significant difference betweenthe operated eyes and non-operated eyes in the progression of retinopathy19. Of 51 operated eyes, 33 (64.7%) achieved an uncorrectedvisual acuity of 20/40 at 1 year postoperatively, and 47 (92.1%) hadimprovement of visual acuity of more than two lines.

In a prospective trial study of50 type 2 diabetes mellitus patients undergoing mono ocular phacoemulsificationby Squirrell et al20, to assess the grade of diabetic retinopathyand diabetic maculopathy in the operated eye and fellow eye pre operatively and12 months post operatively concluded that un complicated phaco emulsificationcataract surgery does not cause acceleration of diabetic retinopathy postoperatively and any progression that is observed probably represents thenatural history of the disease. Wagner et al.28 study also revealedthe same results.

There is still no definite data regarding whetherphacoemulsification will lead to progression of diabetic retinopathy or not.Contradictory results have been obtained in this regard. Not many studies areconducted in Indian population where diabetes prevalence is very high. Thus afollow up study on progression of diabetic retinopathy following uncomplicatedphacoemulsification with adequate sample size in Indian setting standsrelevant.

AIMS AND OBJECTIVES

AIM:

To study the progression of diabetic retinopathy inuncomplicated phacoemulsification with a follow up of 6 months.

OBJECTIVES:

1. To assess the new development of retinopathypost-operatively

2. To study the post-operative progression of stage ofdiabetic retinopathy

3. To assess the post-operative worsening of macularedema

4. To determine the post-operative visual acuity

MATERIAL AND METHODS

STUDY AREA- Giridhar Eye Institute, Cochin.

STUDY POPULATION- Patients with diabetes undergoingphacoemulsification surgery in Giridhar eye institute, Kochi.

Inclusion Criteria:  The patients with established or no diabeticretinopathy in a known case of diabetes mellitus undergoing cataract surgery byphacoemulsification, with no intraoperative complications are included.

Exclusion criteria:  patients with co-existing other retinalpathology, previous intraocular surgeries or inflammation, complications duringphacoemulsification procedure.

STUDY DESIGN- Prospective study

SAMPLE SIZE- 330 participants

STUDY DURATION- One and a half years (From January 2017to June 2018)

METHODOLOGY

Pre-operative evaluation: Visualacuity, anterior segment examination, intra ocular pressure, 78 D examination, indirectophthalmoscopy and colour fundus photography will be done. Optical CoherenceTomography (OCT) will be done if clinical evaluation is suggestive of macularedema or diabetic retinopathy. Fundus Fluorescein Angiography(FFA) will be doneif there is evidence of diffuse macular edema/ severe NPDR/ PDR or prior tostarting laser photocoagulation.

Post-surgery evaluation: Retinalexamination will be done at 3 weeks, 3 months and 6 months.

Evaluation at each visit: Visualacuity, Anterior segment examination, intra ocular pressure, slit lamp examinationby biomicroscopy, indirect ophthalmoscopy and colour fundus photography will beperformed. Optical Coherence Tomography (OCT) will be done if clinicalevaluation is suggestive of macular edema or diabetic retinopathy. FundusFluorescein Angiography (FFA) will be done if there is evidence of diffusemacular edema/ severe NPDR /PDR or prior to starting laser photocoagulation.

The treatment will be decided based on the tests.

The staging of the diabetic retinopathy and diabeticmaculopathy will be done based on ETDRS classification. If OCT is taken, centresparing or centre – involving macular edema will be noted.

The primary outcome measures are new development ofretinopathy, progression of stage of diabetic retinopathy or worsening ofmacular edema based on OCT tests. The secondary outcome measure is post-operative visual acuity.

STATISTICAL METHODS

Descriptive analysis will be carried out using SPSS16  version. Continuous variables will beexpressed in terms of mean and standard deviation. Categorical variables willbe expressed in terms of percentage and frequency. Further statistical test tobe done will be based on the data obtained.

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