Comparison of macular thickness by optical coherence tomography in newly diagnosed type 2 diabetes mellitus patients in their hyperglycaemic and euglycaemic states

INTRODUCTION

Diabetes mellitus (DM) is a chronic metabolic disorder that poses significant risks to multiple organ systems, including the eyes. Among its ocular complications, diabetic retinopathy (DR) remains a leading cause of vision loss worldwide. In India, the prevalence of DR in people with diabetes ranges from 17.6% to 28.2%, and diabetic macular oedema (DME), a vision-threatening form of DR, affects 2.7–11% of diabetics, increasing to over 30% with longer disease duration.^[1,2]

Optical coherence tomography (OCT) has emerged as a non-invasive imaging technique capable of detecting minute structural changes in the retina, particularly the macula. It allows for quantitative assessment of central macular thickness (CMT), which is critical for early diagnosis and monitoring of DME.^[3]

Most previous studies have focused on established diabetic eye disease. In contrast, very few have investigated subclinical macular changes in patients who are newly diagnosed with type 2 DM (T2DM) and have yet to show clinical signs of DR. The pathophysiological changes in the retina may begin early in the disease process due to transient hyperglycaemia, even before visible microvascular alterations occur.^[4]

This study aims to evaluate the changes in CMT in newly diagnosed T2DM patients by comparing OCT measurements during hyperglycaemic and euglycaemic states. The goal is to detect subclinical changes in macular structure that may be reversible with prompt glycaemic control.

MATERIALS AND METHODS

This prospective, hospital-based observational study was conducted over 6 months at a tertiary care ophthalmology centre in India. Ethical approval was obtained from the institutional review board, and all study procedures adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants before enrolment.

Eligible participants were adults aged 18 years or older with a recent diagnosis of T2DM, confirmed within 2 months before enrolment, with no prior history of ocular disease or treatment. Patients were excluded if they had any evidence of ocular surface disease, ocular media opacities hindering high-quality OCT imaging (such as dense cataract), a history of intraocular surgery or retinal laser treatment or systemic comorbidities that could independently affect the retina, including uncontrolled hypertension (uncontrolled hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in diagnosed patients receiving anti-hypertensive treatment) or chronic kidney disease.

Based on their random blood sugar (RBS) and Hb1c level, patients were categorised into two groups: A hyperglycaemic group (RBS ≥ 200 mg/dL with Hb1ac >6.7%) and an euglycaemic group (RBS < 140 mg/dL with hb1ac <5.7% (following medical intervention). All participants underwent a comprehensive ophthalmic evaluation, which included best-corrected visual acuity (BCVA) assessment using a Snellen chart, fundus examination with slit-lamp biomicroscopy using a 90-diopter lens, and indirect ophthalmoscopy. CMT was measured using the Spectralis^® spectral-domain OCT system (Heidelberg Engineering, Germany). CMT was defined as the distance from the internal limiting membrane to the retinal pigment epithelium at the central 1 mm zone of the fovea.

Patients were followed every 10–15 days until glycaemic control was achieved (RBS < 140 mg/dL) through medical therapy comprising oral hypoglycaemic agents and/or insulin. At each follow-up visit, RBS and BCVA were reassessed, OCT imaging was repeated for both eyes, and any retinal changes were documented. Although haemoglobin A1C (HbA1c) was included as a baseline criterion for categorising participants into hyperglycaemic and euglycaemic groups, it was not used as the primary endpoint during follow-up because HbA1c reflects long-term glycaemic status and does not change significantly over short intervals. Since this study aimed to assess acute structural retinal changes during the early phase of glycaemic correction, RBS normalisation was used as the practical and clinically relevant endpoint for short-term follow-up. HbA1c values were recorded at baseline to classify glycaemic status, but serial HbA1c measurements were not feasible within the 10–15-days’ follow-up period.”

All collected data were recorded in Microsoft Excel and analysed using IBM Statistical Package for the Social Sciences Statistics version 26.0. Descriptive statistics were used to summarise demographic and clinical variables. Due to skewed age distribution among study participants, strict age matching between glycaemic subgroups was not feasible. To account for the potential confounding effect of age on macular thickness, age was included as a covariate in the statistical analysis. This adjustment allowed for a more accurate interpretation of the influence of glycaemic status on the retinal thickness parameter. Paired t-tests were conducted to compare CMT values before and after glycaemic normalisation within the same patients. A P < 0.05 was considered statistically significant.

RESULTS

A total of 111 patients were included in the study. The majority were aged 61 years and above, with 36.9% in the 61– 70 years of age group and 29.7% over 70 years, indicating that two-thirds of the patients were older adults. The remaining age distribution was as follows: 2.7% were aged 21–30 years, 3.6% were 31–40 years, 12.6% were 41–50 years and 13.5% were 51–60 years [Graph 1]. Gender distribution showed that 43 patients (39%) were female and 68 (61%) were male [Graph 2].

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Graph 1:

Distribution of patients according to age. NPDR: Nonproliferative diabetic retinopathy

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Graph 2:

Percentage variation of sex.

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Graph 3:

Variations of clinical fundus. NPDR: Non-proliferative diabetic retinopathy

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Among the 111 patients, 75 (68%) had diabetes without any other systemic comorbidities, while 36 (32%) had additional systemic conditions. Visual acuity assessment at presentation revealed that 24.3% of patients had vision between 6/6 and 6/9, 73.9% had vision ranging from 6/12 to 6/24 and only 1.8% had visual acuity between 6/36 and 6/60 [Table 1].

On fundus examination, 56.7% of the eyes were within normal limits, while 22.5% showed mild non-proliferative DR (NPDR), 12.6% had moderate NPDR, 6.3% had severe NPDR and 1.8% had proliferative DR (PDR) [Graph 3].

Follow-up visits demonstrated progressive improvement in both anatomical and clinical outcomes. Tables 2 and 3 indicate a shift toward more patients falling into the normal CMT and mild macular oedema categories. Correspondingly, fundus evaluation showed an increase in the number of patients categorised as within normal limits or with only mild NPDR at the final visit compared to the initial visit. Notably, a worsening of fundus findings was observed in patients with higher HbA1c values [Graph 4].

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Graph 4:

Descriptive statistics of clinical fundus with HbA1c. NPDR: Non-proliferative diabetic retinopathy, PDR: Proliferative diabetic reinopathy.

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Visual acuity also showed improvement over time. Tables 4 and 5 reveal that with continued follow-up and glycaemic control, a substantial proportion of patients improved from a visual range of 6/12–6/36 to 6/6–6/9.

Statistical analysis using a paired t-test demonstrated a significant association (P < 0.05) between CMT and sugar levels, particularly among newly diagnosed diabetic patients. Mean CMT values decreased following medical treatment, from 259 ± 28 µm to 245 ± 30 µm in the right eye; from 255 ± 11 µm to 248 ± 13 µm in the left eye, indicating meaningful anatomical improvement associated with glycaemic control [Table 6].

DISCUSSION

DM remains a leading public health challenge in India, with ocular complications such as DR and DME representing major causes of preventable vision loss. According to the International Diabetes Federation, the age-adjusted prevalence of diabetes in India was 9.6% in 2021 and is projected to rise to 10.4% by 2030.^[5] DR, a microvascular complication of diabetes, is the primary cause of blindness among working-age adults, affecting up to 50% of type 1 and approximately 30% of type 2 diabetic patients over time.^[6] In India, the prevalence of DR ranges from 17.6% to 28.2%, with 2.7% to 11% of patients developing DME. After 25 years of disease duration, the risk of developing DME can rise to as high as 30%.^[1]

Our study focuses on evaluating macular thickness in newly diagnosed diabetic patients before the appearance of clinically detectable DR. This distinguishes our work from most prior studies, which have concentrated on patients with established DME or DR. By assessing CMT longitudinally as patients transition from hyperglycaemia to euglycaemia, our study provides valuable insight into subclinical retinal changes that may precede overt retinal pathology.

Several studies have attempted to explore the relationship between diabetes and CMT in patients without clinical retinopathy, though results have been inconsistent. Demir et al. and Teberik and Esmerligil reported no significant difference in CMT between people with diabetes without DR and healthy controls, and found no correlation between CMT and glycaemic parameters such as fasting glucose or HbA1c.^[7,8] Similarly, the Singapore Indian Eye Study, a population-based analysis, did not find significant differences in CMT between non-diabetic subjects and diabetics without or with only mild DR.^[9]

In contrast, our findings show that even in the absence of clinically apparent retinopathy, patients with hyperglycaemia exhibited a measurable increase in macular thickness. This may reflect early subclinical changes in the neurovascular unit of the retina, underscoring the vulnerability of retinal structures to glycaemic fluctuations before the onset of visible microvascular damage.

Supporting this concept, a recent Nepalese study observed a non-linear trend in macular thickness: CMT was slightly reduced during early diabetes (<1 year) but increased with longer disease duration, indicating possible dynamic remodelling of the retina over time.^[10] Our longitudinal design adds further nuance by demonstrating how early hyperglycaemia may cause subtle thickening of the macula that normalises – or continues to evolve – as glycaemic control is achieved.

Moreover, our findings reinforce the potential role of OCT in detecting early, subclinical retinal changes. Bhende et al.^[11]previously emphasised the utility of OCT as an adjunctive tool for early detection of retinal involvement in diabetic patients. Our results align with their conclusions and suggest that OCT could be effectively incorporated into routine screening protocols even at the time of diabetes diagnosis, rather than waiting for clinical signs of DR to appear.

CONCLUSION

This study highlights early structural changes in the macula associated with hyperglycaemia, even before the clinical onset of DR. Our results underscore the potential value of early OCT screening in newly diagnosed diabetic patients, who may aid in the timely detection and monitoring of retinal alterations.

Recognising the influence of age on macular thickness – typically characterised by age-related thinning – we included age as a covariate in our analysis to control for its impact. This approach enhances the methodological rigor of our study by minimising confounding effects. While complete elimination of age-related variability is not possible, adjusting for age strengthens confidence in our findings.

We acknowledge certain limitations, including a modest sample size and the absence of long-term follow-up, which may affect the generalisability of our results. Future research involving larger cohorts and extended observation periods is needed to validate these findings and explore their relevance for early intervention strategies aimed at preventing diabetic retinal complications. Another limitation is that in our study, HbA1c, although included at baseline for group classification, was not used as a longitudinal endpoint, since meaningful changes in HbA1c require several weeks to months. Future long-term studies incorporating repeated HbA1c measurements may provide a more comprehensive assessment of the relationship between sustained glycaemic control and macular thickness.