Role of Fundus Fluorescein Angiography in Early Diabetic Maculopathy: A Cross-sectional Study

Aim: To assess the role of fundus fluorescein angiography (FFA) for early detection of diabetic maculopathy. Study Design: Prospective Cross-sectional study. Place and Duration: Department of Ophthalmology, unit II Liaquat University of Medical & Health Sciences (LUMHS), Jamshoro, Hyderabad between March 2020 to March 2021. Methodology: Diabetic patients above the age of 20 years were screened by visual acuity recording, fundus, slit-lamp examination, and Fundus fluorescein angiography. Complete ophthalmic detail was obtained from each participant using pre-designed Proforma. Outcomes of the study were recorded. Results: A total of 100 subjects having 200 eyes were observed in the study. There were 53(53%) males and 47(47%) females with a mean age of 54±21.22 years. FFA was done in 124(62%) eyes. Diabetic maculopathy with diabetic retinopathy was higher in moderate nonproliferative diabetic retinopathy (NPDR) 53(42.7%) followed by proliferative diabetic retinopathy (PDR) 22(17.7%), Original Research Article Sahito et al.; JPRI, 34(11A): 38-44, 2022; Article no.JPRI.81743 39 severe NPDR 20(16.1%), and mild NPDR 08(6.5%). Most of the subjects 79(63.7%) had the diffuse type of leakage followed by focal 33(26.6%) and mixed type of leakage. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and Central Macular Thickness (CMT) were improved at the 3 rd and 6 th -month follow-up visit as compared to baseline visit. Conclusion: Fundus fluorescein angiography (FFA), a diagnostic method of diabetic retinopathy is reliable, more accurate, and precise. Our study recommends that diabetic patients should be regularly screened through FFA to save the precious vision of the diabetic population.


INTRODUCTION
Diabetes is a serious health issue in developed as well as in developing countries like Pakistan [1]. Pakistan, at present, stands in the top ten countries in diabetes with a prevalence of 26.3% as reported in the recent second National Diabetes Survey of Pakistan (2016 -2017) [2]. People with diabetes have a higher chance to become blind than non-diabetics, mainly due to diabetes-induced maculopathy and retinopathy [3]. Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR) described that diabetic retinopathy (DR) was present in more than 50% of cases of diabetes. United Kingdom Prospective Diabetes Study (UKPDS) also gave the same results [4,5,6]. In Pakistan, scarce data was found on DR and maculopathy representing between 10.6% and 91.34% for DR [7]. Macula measures 5.5 mm in diameter and it is a round area at the posterior pole. In the center of the fovea, there is a dipped area of 1.5 mm in diameter, called macula [8]. During Fundoscopy macula gives rise to an oval light reflex, while the foveola is the thinnest area of the retina measuring about 0.35 mm in diameter. Outside the foveola, there is a foveal avascular zone [9]. In Diabetic maculopathy there is the involvement of fovea along with edema, hard exudates, or ischemia. Techniques used for screening of DR are slit-lamp biomicroscopy, Fundoscopy, fundus pictures, fundus fluorescein angiography, and optical coherence tomography [10]. FFA detects ischemia, microaneurysms, and intraretinal microvascular abnormalities (IRMA) that are further confirmed on angiogram [11].
There is a marked reduction of visual loss if DR is early detected by FFA [12]. The reduction in glycosylated hemoglobin A1C declines proliferative DR. One percent decline in HbA1c reduces by nineteen percent the eye problems [13]. Proper glycemic control delays dangerous problems of DR. In literature, scarce data was found for search terms of FAZ, aneurysm, and leakage. Very few studies presented FFA findings in diabetic retinopathy. Therefore, this study aimed to present the role of FFA in the early detection of subclinical diabetic maculopathy.

METHODOLOGY
This prospective cross-sectional study was designed at the Department of Ophthalmology, unit II Liaquat University of Medical & Health Sciences (LUMHS), Jamshoro/Hyderabad. The duration of the study was one year between March 2020 to March 2021. A convenience sampling technique was used during the study. Diabetic patients above the age of 20 years coming in Eye-OPD were screened by visual acuity recording, slit lamp, and fundus examination and then further evaluated by FFA. A total of 100 diabetic subjects were selected aged 20 years or above with no history of allergic reaction to fluorescein and having a normal renal profile. Participants with opaque ocular media, allergic to Fluorescein, impaired renal function, hypertension, retinal diseases other than diabetes and those participants who were treated with photocoagulation (macular or Panretinal), intravitreal injections, plana pars vitrectomy, media opacity, venous occlusion, epiretinal membrane, vitreomacular traction were excluded from the study.
Complete ophthalmic detail was obtained from each participant using pre-designed Proforma. It includes a history of eye, ocular examination by Snellen visual acuity was converted to logmar units and assessment of intraocular pressure. One drop of Itrop Plus eye (Cipla Ltd. India -Tropicamide-0.8% and Phenylephrine Hcl-5%) was used to dilate pupils of the eye. Fundus examination was done by the anterior segment of the eye. Fundus Fluorescein Angiography (FFA) of affected eye was done using Topcon Retinal camera -GRC 50DX Germany. Before FFA, for half an hour, each subject was given an intradermal test dose of the 20% Sodium Fluorescein. Radiography was done for 10 to 15 minutes to the accuracy of the examination. The aneurysm size ≤30µm and >30µm was assessed by calibring artery at the superotemporal disc margin (considered as 60µm). The foveal avascular zone (FAZ) size was studied during the arteriovenous phase as compared to optic disc diameter and margin regularity. The presence of focal, diffuse, and mixed leakage was noted. If the leakage occurs from a single aneurysm it is called focal leakage, leakage from dilated capillaries is called diffuse leakage, and from petalloid appearance, leakage is called mixed leakage. Diabetic retinopathy (mild nonproliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and PDR) and maculopathy (mild, moderate, and severe diabetic macular edema (DME)) were clinically classified and graded based on the National Academic Conference of Fundus Diseases and international classification [14,15]. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured by using the Snellen visual acuity chart and Goldman applanation tonometry. Central macular thickness (CMT) was analyzed by optical coherence tomography [16].
All these features were analyzed by using a statistical package for social sciences (SPSS) version 20. Chi-square test and paired t-test were used. P-value < 0.05 was called as significant.

DISCUSSION
In our study, most of the eyes were observed with diffuse maculopathy followed by focal maculopathy and mixed maculopathy. Diabetic maculopathy in subjects with diabetic retinopathy was higher in moderate NPDR followed by PDR, severe NPDR, and mild NPDR. The frequency of the focal type of leakage was found higher compared with diffuse and mixed types of leakage. Collectively, BCVA, IOP, and CMT were improved at the 6-month follow-up as compared to the baseline visit.    [19].
Our study is unique to present FFA in diabetic maculopathy in this part of the world thus highlighting the strength of our research. In our study, diffuse leakage was higher similar to Mehboob et al study observed diffuse leakage as a common finding [20]. Syed SH et al also found an increased prevalence of diffuse leakage of maculopathy in people with diabetic retinopathy followed by facal and ischemic types of leakage [21]. However, a recent study by Rasquinha et al found a high frequency of the focal type of leakage unlike our study and other previous ones [15]. We also observed functional improvement in BCVA, IOP, and CMT at six months follow up which is a good achievement in our resource constraint society similar to recent study findings on diabetic macular edema [16]. Most of the participants had diabetes-associated risk factors such as hypertension and dyslipidemia which are major causes of developing eye complications and should be treated earlier. We did not find the association of FFA with age, gender, and duration of diabetes as previous studies reported no significant association with these kinds of parameters. However, most of our study subjects were males, had average age between 51-60 years, and had five years or more duration of diabetes similar to previous studies [17].
For FAZ visualization, the disruption spectrum involving the FAZ includes FAZ area or diameter enlargement, disruption, and widening of terminal vessels [12]. Screening program should be developed for the early detection of diabetic maculopathy, as a vision of diabetic patients can be saved. With the advancement of technology, digital photography with telemedicine should also be promoted [12]. A study limitation was consistent with the small sample size in the large population, resulting in no correlation between FFA with OCT, which is mostly used to quantify macular edema.

CONCLUSIONS
FFA, a diagnostic method of diabetic retinopathy is reliable, more accurate, and precise. Our study highly recommends the screening of diabetic patients in the early stages through FFA to save the precious vision of the diabetic population.

CONSENT
Each selected participant was pre-informed and written informed consent was taken.

ETHICAL APPROVAL
Ethical approval for the study was obtained from the ethics committee of LUMHS.