Introduction

The International Federation of Diabetes has informed that 415 million adults worldwide have diabetes and that by 2040, the figure would be about 642 million. (IDF, 2015) The World Health Organisation (WHO). The WHO Global Diabetes Survey indicates that the number of people who have diabetes has quadrupled to 422 million individuals since 1980. (WHO, 2016) International age-standardised adult diabetes incidence was estimated to be 9.8% between men and 9.2% between women in 2008, rising from 8.3% and 7.5% in 1980. (Danaei et al., 2011)

The International Diabetes Federation reports its 425 million people with diabetes worldwide, and 82 million of these are present in the South East Asian region. India is one of the countries in the SEA area and amounts to 72,946 cases of diabetes. (Roy, 2018) The incidence of insulin-dependent diabetes mellitus (DDM) or type 1 diabetes is 10-15% of the diabetic population. The urban population in the developing world is estimated to increase between 2000 and 2030. The single most significant structural trend responsible for the incidence of diabetes in this region of the world tends to be a rise in the number of people over 65 years of age. (Rathmann & Giani, 2004)

The first-ever documented evidence of diabetes came from a discovery made by a German archaeologist named George Ebers which was papyrus in Egypt in the 19th century and ever since then it's known as the Ebers Papyrus in his honour. In ancient India, diabetes was known as prameha [pra -excess, meha -urine], a term used to refer to the disease even today in specific Indian languages.

Diabetes is not a new disease, the Charaka Samhita, dating back to 1500 bc, describes prameha in great detail. It recognises 20 types of prameha which if not treated, can lead to madhumeha [madhu- honey, meha- urine, literally sweet urine, unambiguous description of diabetes. It is accepted generally that the term diabetes means "siphon", and was defined by aretaeus of Cappadocia, about the polyurea characteristic of uncontrolled disease. The word “siphon” means sucking water out from the body through the urine. (Diamond, 2003)

AIM AND OBJECTIVES

Aim

• Retinopathy evaluation clinically and angiographically in diabetic patients less than ten years of diabetic age.

Objectives

• To study diabetic retinopathy clinically and angiographically.

• To study retinal changes in the various duration of diabetes.

REVIEW OF LITERATURE

Diabetic retinopathy (DR) is a vascular disorder that impacts people with diabetes mellitus. DR is the most severe microvascular complication of diabetes. (Tarr, Kaul, Chopra, Kohner, & Chibber, 2013) Thousands of people are impaired by DR, including about one-fourth of vision-threatening diseases. The risk of having DR is related to the time of the illness. The possibility of retinopathy during puberty decreases.

The retina is a multi-layered sheet composed of neurons, photoreceptors, and support cells. It is a metabolically, very active organ; that is why it is more prone for ischemia and nutrient imbalances. The outer one-third of the retina receives its blood supply from the choriocapillaris, a vascular network that lies between the retina and sclera. The inner two-thirds of the retina is supplied by branches of the central retinal artery, which comes from the ophthalmic artery (the first branch off of the internal carotid artery. The central retinal artery exits out of the optic nerve, and its branches arch temporally both above and below the macula (the sensitive region of the retina responsible for central vision).

Classification

DR is classified into two major categories: proliferative and non-proliferative. The term "proliferative" applies to neo vascularisation (abnormal development of the blood vessels) of the eye, "non-proliferative" implies without retinal neovascularisation. When the disease advances, proliferative diabetic retinopathy (PDR) may evolve, and is characterised by the occurrence of neo vascularisation and has a more substantial capacity for severe visual implications.

Symptoms

When disease may be ineffective, patients are typically asymptomatic before the late stage of the disorder. The late symptoms of DR differ depending on the cause. Bleeding in vitro may cause a sudden vision loss. Macular oedema and ischemia are two common causes of reduced vision.

Treatment Options

NPDR is usually managed by optimising the general health of the patient. The best treatment for DR is tight glucose control (DCCTRG 1993) with its development and prevention. Patients should maintain an HbA1c≤7%. BP management has also been shown to reduce disease progression (UKPDSG 1998), and patients should be counselled to stop smoking. Ophthalmologists should intervene if there is a clinically significant macular oedema (CSME) with NPDR. Inductive micro-aneurysms are localised, often using fluorescein angiography, and then treated directly with laser therapy. If the leak is more diffuse, the grid laser burn may slow oedema. Finally, several off-label medical options are available, such as intra-vitro injection of triamcinolone and antibodies against VEGF such as Lucentis® or Avastin®. Once a patient has developed PDR, several treatment modalities are available.

Retrospective testing

Fluorescence angiography (FA) can be used to document retinal vessel exclusion and/or leakage definitively. During FA, a fluorescent dye is injected intravenously, and with a special camera, photographs of the fundus are taken over several minutes, while the vessels are scented. The test is best used to guide the treatment of CSME, and not for diagnosis (AAO 2008). CSME was diagnosed only by the clinical appearance. By direct and indirect ophthalmoscopy, diabetic retinopathy can be evaluated. Various imaging modalities are depending on the manifestation of diabetic retinopathy. Other techniques include colour fundus photography, FFA, B-scan ultrasonography, and optical coherence tomography (OCT). Colour fundus photography is widely used, with advances there are digital images available which help to see the progression of the disease over time and counselling, image magnification is also possible. There are three types of fundus photography: Standard, wide-field, and stereoscopic. Standard macular fundus photography captures 30° of the posterior pole of the eye, which includes the macula and the optic nerve1. It is easy to operate and highly available and helps in the documentation and can identify hard exudates. It doesn't confirm clinically significant macular oedema (CSME). (Early Treatment Diabetic Retinopathy Study Research Group, 1987)

Paper Review

Mulgund and Chandran (2017) did an analytical study for 12 months. The initial examination was included fundus examination with the help of direct ophthalmoscope. The research was done among 50 DM patients who attended the OPD. The study found that the Fundus Fluorescein Angiography (FFA) is a useful diagnostic procedure. Also, they concluded that the procedure is helpful in treatment, diagnosis, documentation as well as to maintain a record of diabetic retinopathy staging, response of the treatment and depending on that follow up can be decided.

A study was done by Veshal Madan, which was done to see the efficacy of FFA and OCT in the diagnosis of DME, i.e. Diabetic macular oedema. It was a prospective study which used purposive sampling technique on 308 eyes of 154 type II DM patients to compare the detection potential between two popular retinal diagnostic procedures, SD-OCT a non-invasive technique versus FFA invasive method for DME. The study included standard parameters such as focal macular oedema, diffuse macular oedema and mixed oedema with cystoid type with FFA. Subsequently, DME classification was used for the presence of subretinal fluid, intraretinal oedema and mixed oedema, which was diagnosed on SD-OCT for the same patients. Clinical features in DME using reference EDTRS scale of measurement was used. The study found that noninvasively 305(99.1%) eyes were detected positive for various type of DME by SD-OCT, while 282(91.6%)eyes were detected positive by FFA. The prevalence of the kinds of DME such as cystoids, diffuse, focal and mixed was 7.8%,13%,7.1%and 63.7%respectively as diagnosed with FFA. The prevalence of Sub Retinal Fluid(SRF), Intra Retinal oedema (IRE)and the mixed type was 4.9%,3.6%and 90.6%respectively as diagnosed with SD-OCT.FFA did not detect DME in 8.4%of eyes in the overall study population. Whereas, SD-OCT was unable to detect DME in 0.9%of eyes. In our study, the overall performance of SD-OCT was superior for the detection of DME (diabetic macular oedema) when compared with FFA. It concluded that the diagnostic potential and efficacy of SD-OCT over FFA in reliable and safe detection of DME in Type II Diabetic Mellitus patients was more and was smooth and comparable to diagnostic findings of FFA specifically in cases of subretinal macular oedema and also choroidal oedema due to DME by SD-OCT.

Materials and Methods

Study Design

Diagnostic cross sectional study

Study Site

A tertiary care hospital and teaching institute in western Maharashtra. (Krishna Institute of Medical Sciences, Karad)

Study Period

November 2016 – May 2018

Sample size

According to a study conducted by (Ling, Ramsewak, Taylor, & Jacob, 2002), prevalence of Diabetic Retinopathy in type 2 DM patients was 6.7%

So, p = 6.7%

Using formula for sample size (n) calculation,

where, p = 6.7% = 0.067

q = 1 - p = 0.933

Taking e, absolute error of 5%, e = 0.05

So,

0.05 x 0.05

A minimum of 97 patients will be included, rounding it up to 100. So, N = 100, that's 100 patients will be included in our study, i.e. 200 eyes will be studied.

Source of Data & Data Collection

Diabetic patients of less than ten years of diabetic age coming to the ophthalmology OPD and admitted in the wards of the parent medical college were included.

Informed written consent of the patient was taken, and proforma of the study was explained to the patients. The data was collected using a pre-evaluated semi-structured questionnaire.

Demographic profile of the patients, including age, gender was undertaken. History of the patients was taken, and the examination was done. Required laboratory investigations were also done in Table 1, Table 2, Figure 1, Figure 2, Figure 3 and Figure 4.

Patients were categorized as-

• Patients of 0-1 year of diabetes

• Patients of 1-5 year of diabetes

• Patients of 5-10 year of diabetes

Ocular examination included

• Visual acuity assessment.

• Anterior segment examination

• Posterior segment examination includes the vitreous and retinal examination

Detail fund us examination under mydriasis will be performed with keeler direct ophthalmoscope, indirect ophthalmoscope with +20 D volk lens (Appasamy associate) and Topcon slit lamp with volk +90 D/+78 D lens along with FUNDUS PHOTOGRAPHY was performed and fundus fluorescein angiography for which Topcon TRC NW8F Non-Mydriatic Retinal Camera was used Physician fitness was taken before performing FFA FFA Procedure was explained. Informed written consent of the patient was taken.

All the emergency medications to treat reactions were kept ready Fluorescein injection 20% (FLURES) was used for doing FFA. The eye drop (phenylephrine + tropicamide) was used to dilate the pupil.

Early Treatment Diabetic Retinopathy Study (ETDRS) criteria were used for classifying Diabetic retinopathy

Statistical Analysis

Data Collected was entered in Microsoft Excel Data is represented in frequencies and percentages, charts and graphs. Appropriate statistical tests were applied using SPSS software version 21 for analysis.

Associations were found by chi-square test wherever applicable. Kappa statistics was used to detect the agreement between the Ophthalmoscopy and Fluorescent Fundus Angiography.

OBSERVATIONS AND RESULTS

The study had most of patients from the age group of 51 -60 years (48%). There were 28% more than 60 years and 24% who belonged to 40-50 years of age. The mean age was 55.89 ± 6.10 years in Table 3.

Out of total 100 patients, there were 56% males and 44% females. The ratio was 1.27- Males: Females in Table 4.

The study had majority 35% who suffered from diabetes < 1 year. There were 33% who had diabetes for 1-5 years and 32% who had diabetes for 5-10 years duration. The mean diabetic age was 3.92 ± 3.00 years in Table 5.

In our study, we found majority 65% were having fasting blood sugar(FBS) levels >126 mg/dl, while few cases 14% with levels < 100, and rest 21% with FBS levels of 100 to 125 mg/dl. The mean FBS level was 141.72 ± 37.68 mg/dl in Table 6.

In our study 51.5 percent eyes had visual impairment between 6 / 18 – 6 / 60, 40 percent eyes with no impairment and 17 percent eyes with severe visual impairment in Table 7.

In our study, we had majority 52% cases had no diabetic retinopathy and out of rest 48% cases, there were 24% who had severe NPDR and 18% had moderate NPDR and3.5% who had mild NPDR. Proliferative diabetic retinopathy was observe in 2.5 % cases in Table 8.

On FFA findings, 47% of cases had no retinopathy, the rest 53% had retinopathy. There were 15.5% with moderate NPDR, 25.5% with severe NPDR and 8% with mild NPDR. Proliferative retinopathy seen in 4 % cases in Table 9.

The study shows association between the age and FFA findings. The association was highly significant statistically. In the age group of 40 to 60, as the age increased the proportion of NPDR increased and also there was increased proportion of PDR with increase in age. (p<0.0001) in Table 10.

The association between sex and Ophthalmoscopy Findings was not found to be significant in our study (p = 0.850) in Table 11.

In our study we have seen association between duration of diabetes and ophthalmoscopic findings. The proportion of Diabetic retinopathy increased with increasing in duration of diabetes. (p<0.0001) in Table 12.

In our study we have seen association between duration of diabetes and fundus fluorescence angiography findings. The proportion of Diabetic retinopathy increased with increasing diabetic age. (p<0.0001) in Table 13.

The association between HbA1c and FFA Findings was found to be highly significant in our study (p <0.0001) n Table 14.

Out of total 200 cases, on ophthalmoscopy, 96 cases (48%) were found to have Diabetic retinopathy, while on FFA 106 cases (53%) were found to have Diabetic retinopathy. These additional 5% cases were diagnosed on FFA. There was not a single case diagnosed as not having any Diabetic retinopathy on FFA which showed changes of Diabetic retinopathy on Ophthalmoscopy in Table 15.

The above table shows similar findings of diabetic retinopathy on both ophthalmoscopic and FFA findings. The patients were divided into having retinopathy & absence of retinopathy by both the tests, almost always. The statistical test showed agreement to be 93.5% and kappa value was 0.88 which is referred to as strong agreement in Table 16.

On ophthalmoscopy, we found 96 eyes (48%) having any kind of Diabetic retinopathy, while on FFA, we found 106 eyes (53%) with Diabetic retinopathy in Table 17.

Mild NPDR was seen in 7 eyes (3.5%) in ophthalmoscopy while on FFA total 16 (8%) eyes had shown mild NPDR. Similarly, severe NPDR was found in 48 (24%) eyes on ophthalmoscopy while on FFA, severe NPDR was seen in 51(25.5%) eyes. In the case of PDR, 5 (2.5%) eyes were diagnosed as PDR on Ophthalmoscopy while on FFA, we found 8 (4%) eyes of PDR. Only in case of Moderate NPDR, on ophthalmoscopy, we found more instances as compared to FFA, 36 eyes (18%) and 31 eyes (15.5%) respectively.

When we compared the association between the absence of diabetic retinopathy and the types of retinopathy, we found a significant association with the mild NPDR (p = 0.045). At the same time, there was no any significant association with moderate NPDR (p = 0.864), severe NPDR (p = 0.511) or PDR (p = 0.326).

Discussion

The World Health Organization (WHO) has estimated that the number of adults with Fundus disorders in the world would increase alarmingly. Globally, it is estimated that there are 38 million people who are blind. In India: 9 million people are blind, which comes to one-fifth of the total in the world (Murthy & Gupta, 2005; Thylefors, Negrel, & Pararajasegaram, 1995). (Approx. 8-9 blind people/ 1000 population) The prevalence of blindness in India, as determined by the three major population-based surveys and one rapid assessment of avoidable blindness is as follows 1.38% in ICMR (1971-74), 1.49% in WHO-NPCB (1986-89), 1.1% in NPCB (2001-2002), 1% in RAAB (2006-2007) (Neena, Rachel, Praveen, & Murthy, 2008).

The prevalence of blindness due to posterior segment diseases in India was 4.7% of total blindness according to a national survey (NPCB) of 2001-2002 and 3% of total blindness as per the rapid assessment of avoidable blindness (RAAB) 2006-07 survey (Nazimul, Rohit, & Anjli, 2008).

The trend of retinal blindness has changed its pattern over the years in developing countries (Resnikoff & Keys, 2012). Diabetic retinopathy and ARMD are becoming one of the major causes of blindness (Kohner & Sleightholm, 1986).

The study had most of the participants from the age group of 51 to 60 years, with a mean of 55.89 ± 6.10 years. Ling et al. (2002) had higher age group, and the mean age was 72.1 years. While in Sumi S. et al., had a younger age group, and the mean age was 52.9 years. Mulgund, et al (Mulgund et al., 2017; The Diabetes Control and Complications Trial Research Group, D M Nathan, S Genuth and J Lachin, 1993) had comparable age group of 55.65 years as in our study. (Khalaf, Al-bdour, & Al-till, 2007) had mean age of 54.91 years similar to our research. The majority that is 56% of patients were males, And females were 44%. Similar findings were found in Mulgund et al. study, but (Villalpando et al., 1997) had more number of females as compared to males.

A study by (Noorani & Cheema, 2008) studied the role of Fundus Fluorescein Angiography in Pre-proliferative Diabetic Retinopathy. The study did Fundus fluorescein angiography of 25 patients having PPDR unilaterally or bilaterally was performed. In the study, Fundus fluorescein angiography was used as an essential diagnostic tool to show the exact location and extent of vascular changes of PPDR. In the current study also we did the same, used Fundus fluorescein angiography to check for the sensitivity for diagnosing early changes in fundus of diabetic patients.

In (Mulgund et al., 2017) study, they found out one crucial predictive factor that is reduced blood sugar level. The associations between HbA1c with Ophthalmoscopy Findings and FFA Findings were significant in our study (both with a p <0.0001).

Parallel results were given by diabetes control trial research group (Khalaf et al., 2007), who found out that increased levels of glycosylated haemoglobin were associated with a significant increase in the progression of DR. Majority of the patients had impairment of vision which was 6/18 - 6/60 who were 51.5% of these people. There were 40% with no impairment and 8.5% with severe vision impairment.

Conclusion

Diabetic retinopathy is one of the preventable complications of diabetes, if diagnosed early and correctly, it can prevent severe complications in patients. Our study compared different factors about diabetes and the development of diabetic retinopathy. We also compared the Ophthalmoscopy and FFA tests to diagnose diabetic retinopathy. We found out that there was a significant association between age groups of the patients, duration of diabetes, and the development of diabetic retinopathy. No significant association with the gender of the patients was seen in the development of retinopathy. In patients less than five years of diabetic age or those who are at the early stage of diabetic retinopathy, we observed that rapid pathological changes which could not be seen on ophthalmoscopy were evident on FFA. So by Early detection of diabetic retinopathy, we can help to stop further progression of retinopathy. There was strong agreement between the Ophthalmoscopy and FFA in diagnosing diabetic retinopathy, while FFA has diagnosed more number of cases with diabetic retinopathy which had missed out on ophthalmoscopy. FFA is a better diagnostic tool for diagnosing retinopathy as compared to ophthalmoscopy.