Systemic hypertension is one of the most prevalent chronic diseases worldwide and a leading modifiable risk factor for cardiovascular morbidity and mortality.[1] Beyond its well-established effects on the heart, kidneys, and cerebrovascular system, hypertension profoundly impacts the eye, causing a spectrum of structural and functional changes collectively termed as target-organ damage.[2] The retina, with its unique vascular anatomy and direct optical accessibility, provides a window to observe the microvascular consequences of sustained elevated blood pressure, making ophthalmoscopic examination an invaluable tool for assessing both ocular and systemic hypertensive damage.[3]

Hypertensive retinopathy is the most common ocular manifestation of systemic hypertension, with prevalence rates ranging from 28.5% to 77.1% among hypertensive individuals depending on disease severity, duration, and control. Studies have demonstrated that approximately 2% to 17% of adults without diabetes show retinal changes such as microaneurysms, hemorrhages, and arteriovenous nicking attributable to hypertension.[4] These retinal vascular alterations result from two distinct pathophysiologic mechanisms: chronic arteriosclerotic changes characterized by vessel wall thickening, increased light reflex, and arteriovenous crossing abnormalities; and acute vasospastic changes manifesting as focal or generalized arteriolar narrowing, retinal hemorrhages, cotton-wool spots, and in severe cases, papilledema.[5,6]

Several classification systems have been developed to grade the severity of hypertensive retinopathy and correlate fundoscopic findings with systemic disease burden. The Keith-Wagener-Barker classification, proposed in 1939, stratifies hypertensive retinopathy into four grades: Grade 1 (mild generalized arteriolar constriction), Grade 2 (definite focal narrowing with arteriovenous nicking), Grade 3 (Grade 2 plus hemorrhages, cotton-wool spots, and hard exudates), and Grade 4 (Grade 3 plus papilledema). Subsequently, the Modified Scheie classification and the simplified Mitchell-Wong system have been introduced to improve clinical applicability and prognostic correlation. These grading systems not only facilitate clinical documentation but also serve as predictors of cardiovascular risk, with higher grades associated with increased incidence of stroke, myocardial infarction, congestive heart failure, and mortality.[7-10]

Beyond retinopathy, systemic hypertension can cause hypertensive choroidopathy, characterized by dysfunction of the choroidal circulation leading to ischemic damage of the choriocapillaris, retinal pigment epithelial changes, and serous retinal detachment. [11,12]Hypertensive optic neuropathy presents as optic disc swelling with flame-shaped hemorrhages at the disc margin, blurred disc margins, and congested retinal veins, and when accompanied by papilledema, indicates malignant hypertension requiring urgent management.[13] Additionally, chronic hypertension predisposes patients to secondary retinal vascular occlusions including central and branch retinal artery occlusion, central and branch retinal vein occlusion, and retinal arterial macroaneurysms, all of which can lead to significant visual morbidity.[ 14,15]

The clinical significance of detecting and documenting hypertensive ocular manifestations extends beyond ophthalmology. Recent evidence using advanced imaging modalities such as optical coherence tomography angiography (OCTA) has demonstrated that hypertensive patients show decreased macular vessel density, increased foveal avascular zone, and reduced retinal nerve fiber layer thickness compared to normotensive controls, suggesting that these microvascular changes may serve as biomarkers for systemic end-organ damage and cardiovascular risk stratification.[16] Furthermore, the presence of moderate to severe hypertensive retinopathy has been associated with an increased risk of stroke independent of blood pressure levels, emphasizing the prognostic value of fundoscopic examination in risk assessment.[17,18]

Despite the established association between systemic hypertension and ocular manifestations, there remains considerable variation in the reported prevalence and severity of hypertensive ocular changes across different populations, possibly reflecting differences in hypertension duration, adequacy of blood pressure control, ethnicity, and coexisting risk factors such as diabetes mellitus and dyslipidemia.[19,20] Understanding the spectrum and frequency of ocular manifestations in hypertensive patients is essential for early detection, appropriate referral, and timely intervention to prevent vision-threatening complications and to identify patients at high risk for systemic cardiovascular events. This cross-sectional study was therefore undertaken to systematically evaluate the prevalence, types, and severity of ocular manifestations in patients with systemic hypertension presenting to our tertiary care center, and to correlate these findings with the duration and control of hypertension.

Study Design and Setting

This cross-sectional observational study was conducted in the Department of Ophthalmology over a period of 12 months. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants after explaining the nature and purpose of the study in their native language.

Sample Size Calculation

Based on calculation, a minimum sample size of 384 patients was required. Accounting for potential dropouts and incomplete data, a total of 400 patients with systemic hypertension were enrolled in the study.

Study Population

Inclusion Criteria:

• Patients aged 18 years and above
• Diagnosed cases of systemic hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on at least two separate occasions, or patients on antihypertensive medications)
• Duration of hypertension at least 6 months
• Willing to provide informed consent and undergo detailed ocular examination

Exclusion Criteria:

• Patients with pre-existing ocular pathology including glaucoma, age-related macular degeneration, diabetic retinopathy, retinal vascular occlusions, and optic neuropathy of other etiology
• Media opacities preventing adequate fundus visualization (dense cataracts, corneal opacities, vitreous hemorrhage)
• History of previous ocular surgery or laser treatment
• Pregnant and lactating women
• Patients with uncontrolled diabetes mellitus (HbA1c >7.5%)
• Renal insufficiency (serum creatinine >2 mg/dL)
• Acute medical illnesses or hospitalization within the past 3 months
• Patients who refused consent or were unable to cooperate for examination

Patient Selection and Recruitment

Consecutive patients diagnosed with systemic hypertension attending the Medicine outpatient department and referred to the Ophthalmology department for routine screening were enrolled in the study. Detailed history was obtained including age, gender, duration of hypertension, current antihypertensive medications, compliance to treatment, associated comorbidities, and symptoms of visual impairment.

Blood Pressure Measurement

Blood pressure was measured using a standardized protocol following the guidelines of the American Heart Association. Patients were asked to rest in a sitting position for at least 5 minutes in a quiet environment before measurement. Blood pressure was measured in the right arm using a calibrated mercury sphygmomanometer or validated automated electronic blood pressure monitor with an appropriate-sized cuff. Three readings were taken at 5-minute intervals, and the average of the last two readings was recorded as the blood pressure for the study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were documented.

Patients were classified based on blood pressure control as:

• Controlled hypertension: SBP <140 mmHg and DBP <90 mmHg
• Uncontrolled hypertension: SBP ≥140 mmHg and/or DBP ≥90 mmHg

Ophthalmic Examination

All patients underwent comprehensive ophthalmic evaluation by a single trained ophthalmologist to minimize interobserver variability. The examination protocol included:

1. Visual Acuity Assessment: Best-corrected visual acuity (BCVA) was recorded using Snellen's chart at 6 meters and converted to LogMAR units for statistical analysis.
2. Anterior Segment Examination: Slit-lamp biomicroscopy was performed to rule out anterior segment pathology and assess media clarity.
3. Intraocular Pressure Measurement: Intraocular pressure was measured using Goldmann applanation tonometry.
4. Dilated Fundus Examination: Pupils were dilated using tropicamide 1% eye drops instilled twice at 10-minute intervals. After achieving adequate mydriasis (pupil diameter ≥6 mm), detailed fundus examination was performed using indirect ophthalmoscopy with +20D lens and slit-lamp biomicroscopy with +90D lens. Both eyes were examined, and the eye with more severe retinopathy was considered for grading and analysis.
5. Fundus Photography: Digital color fundus photographs centered on the optic disc and macula were obtained using a fundus camera (specify model) after pupillary dilation. Images were stored digitally for documentation and subsequent review.

Grading of Hypertensive Retinopathy

Hypertensive retinopathy was graded using the Keith-Wagener-Barker (KWB) classification system, which has been widely used in clinical practice and research:

Grade 0 (No retinopathy): No detectable retinal vascular changes

• Grade 1 (Mild retinopathy): Mild, generalized constriction of retinal arterioles; increased arteriolar light reflex (silver wiring or copper wiring)
• Grade 2 (Moderate retinopathy): Definite focal narrowing of retinal arterioles; arteriovenous (AV) nicking or AV crossing changes
• Grade 3 (Severe retinopathy): Features of Grade 2 plus flame-shaped retinal hemorrhages, cotton-wool spots (nerve fiber layer infarcts), and hard exudates
• Grade 4 (Malignant retinopathy): Features of Grade 3 plus papilledema (optic disc swelling) and/or macular star exudates
• Additionally, the simplified Mitchell-Wong grading system was also applied for comparison:

Mild retinopathy: Arteriolar narrowing, AV nicking, or arteriolar wall opacity

• Moderate retinopathy: Hemorrhages, microaneurysms, cotton-wool spots, or hard exudates
• Severe retinopathy (Malignant hypertension): Moderate retinopathy plus optic disc swelling

Other retinal findings documented included presence of retinal arteriolar macroaneurysms, retinal vein occlusions, retinal artery occlusions, and macular edema.

Laboratory Investigations

Relevant laboratory investigations were obtained from patient records or performed during the study visit, including:

• Fasting and postprandial blood glucose levels
• Glycosylated hemoglobin (HbA1c)
• Lipid profile (total cholesterol, HDL, LDL, triglycerides)
• Serum creatinine and estimated glomerular filtration rate (eGFR)
• Complete blood count
• Electrocardiogram (ECG) for assessment of left ventricular hypertrophy
• Data Collection and Variables

A structured proforma was used to collect the following data:

Demographic variables: Age, gender, occupation, socioeconomic status

Clinical variables: Duration of hypertension, blood pressure readings, current medications, medication compliance, family history of hypertension, smoking and alcohol consumption, body mass index (BMI)

Ocular variables: Best-corrected visual acuity, grade of hypertensive retinopathy, specific retinal findings, intraocular pressure

Laboratory parameters: Blood glucose, HbA1c, lipid profile, renal function tests

A total of 400 patients with systemic hypertension were enrolled in the study, with a mean age of 54.8 ± 10.6 years and male predominance (58%). The mean duration of hypertension was 7.4 ± 5.1 years, and 54% of patients had uncontrolled blood pressure at presentation. Diabetes mellitus and dyslipidemia were present in 24% and 29.5% of patients, respectively (Table 1). Hypertensive retinopathy was detected in 248 patients (62%), with the distribution as follows: Grade 1 in 106 patients (26.5%), Grade 2 in 88 patients (22%), Grade 3 in 42 patients (10.5%), and Grade 4 in 12 patients (3%), while 152 patients (38%) showed no retinopathy (Table 2). The prevalence and severity of hypertensive retinopathy showed significant association with blood pressure control and duration of hypertension; among patients with uncontrolled hypertension, 81.5% had retinopathy compared to 39.1% in the controlled group (p<0.001), and moderate-to-severe retinopathy (Grades 3-4) was present in 20.4% versus 5.4%, respectively (p<0.001). Similarly, retinopathy was observed in 34.8% of patients with hypertension duration <5 years, 61.1% with 5-10 years duration, and 84.7% with >10 years duration (p<0.001) (Table 3). Specific retinal findings included arteriolar narrowing (26.5%), increased arteriolar light reflex (24.5%), arteriovenous nicking (22%), flame-shaped hemorrhages (12%), cotton-wool spots (10.5%), and hard exudates (9.5%). Other sight-threatening complications documented were branch retinal vein occlusion (4%), macular edema (7%), hypertensive choroidopathy (2.5%), and papilledema (3%) (Table 4). Visual acuity analysis revealed that patients with severe retinopathy (Grades 3-4) had significantly worse visual outcomes, with 31.5% experiencing visual impairment (worse than 6/18) compared to only 6.9% in those with mild or no retinopathy (Grades 0-2), and the mean LogMAR best-corrected visual acuity was 0.34 ± 0.28 versus 0.12 ± 0.18, respectively (p<0.001) (Table 5). Multivariate analysis identified duration of hypertension >10 years, uncontrolled blood pressure, and presence of diabetes mellitus as independent predictors of hypertensive retinopathy.

Table 1: Demographic and Clinical Characteristics

Table 2: Prevalence and Distribution of Hypertensive Retinopathy

Table 3: Association of Hypertensive Retinopathy with Blood Pressure Control and Duration

Table 4: Specific Retinal Findings in Hypertensive Patients

Table 5: Visual Acuity Status and Association with Severity of Retinopathy

Ocular manifestations in systemic hypertension vary across cross-sectional studies but consistently highlight retinopathy, arteriolar narrowing, and choroidopathy as key findings linked to blood pressure control. For instance, one study found higher retinopathy prevalence (up to 14%) in uncontrolled hypertension compared to controlled cases (6%), aligning with others reporting arteriovenous nicking in 10-20% of patients. [5,21,22] These patterns underscore the retina's role as a microvascular damage indicator, though imaging advances like OCT reveal subtler changes earlier than traditional fundoscopy. Cross-sectional data show retinopathy signs in 5-15% of hypertensives overall, rising to 30% in severe cases (e.g., Keith-Wagener grade III/IV), similar to findings in population-based cohorts like the Beaver Dam Eye Study (incidence 2-6% over 5 years in treated patients). Arteriolar narrowing appears in 40-60% of long-term hypertensives, comparable to rates in European studies (45-55%). Choroidal changes, including Elschnig spots, occur in 10-25% during hypertensive crises, matching acute-phase reports.[23,24,25] Keith-Wagener-Barker grades correlate with systemic risk: mild (grade 1-2) in 70-80% of mild hypertensives versus severe (grade 3-4) hemorrhages/exudates in <10%, echoing Wong and Mitchell's microvascular assessments. Recent OCT studies report foveal thickening in 20% of cases, higher than fundoscopic detection (12%), indicating imaging's edge.[5,9,22,26]Retinopathy doubles stroke risk (OR 2.1-2.5), consistent across meta-analyses, while optic neuropathy links to 1.5-fold cardiovascular mortality. BP reduction mitigates 50-70% of lesions, per intervention trials.[23,27,28]

Hypertensive ocular disease shows a consistent pattern across cross-sectional studies: hypertensive retinopathy with arteriolar changes, plus rare but serious complications like choroidopathy and optic neuropathy, correlates with blood pressure burden and duration. Higher retinopathy grades predict greater systemic risk, including stroke and cardiovascular mortality, while BP reduction can substantially mitigate retinal lesions. Advanced imaging (OCTA, OCT) detects microvascular changes earlier than conventional fundoscopy, offering potential for improved risk stratification and timely systemic intervention. Overall, the eye serves as a valuable surrogate for systemic vascular health in patients with hypertension.

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