Systemic Risk Factors and Clinical Profile of Retinal Vein Occlusion in A Tertiary Eye Care Hospital in Northern Uttar Pradesh-A Case Control Study

: Objective: To assess the various risk factors and clinical presentation in patients with Retinal Vein Occlusion presenting to a tertiary eye care hospital in Uttar Pradesh. Study design and type: case control study, retrospective study. Methodology: The study comprised patients with retinal vein occlusion (100) who had been identified using accepted diagnostic standards and who met the prerequisites for participation. The healthy controls (100) who did not have retinal vein occlusion. Patients ranged in age from 18 to 70, and those with liver illness, dense media opacities, retinal vasculitis, kidney dysfunction, a history of systemic vasculitis, or past systemic vascular events were excluded. Result: A total of 200 people have signed up for this study.in which 100 patients (50%) had retinal vein occlusion (case group) and 100 patients (50%) were healthy (control group).in the study of 100 patients, 43% had branch RVO, 54% had central RVO, and 3% had hemi RVO. The age of patients who presented with retinal vein occlusion varied from 21 to >80. Hypertension was significantly higher in cases (61.0%) as compared to controls (32.0%). Moreover, the mean systolic and diastolic BP were 149.57 ± 22.98 and 92.12 ± 11.66 in cases, and 137.64 ± 13.41 and 83.21 ± 7.60 in the control group. The percentage of cases with diabetes in this study was significantly higher (32.0%) than in controls (13.0%). Conclusion: In our study found that 43% of patients had BRVO, 54% had CRVO, and 3% had hemi-RVO. The males were more frequently affected by RVO. Diabetes and hypertension were significantly more common in RVO patients. Our findings imply that dyslipidaemia plays a major role in the aetiology of disorders of the retinal vascular system. Disorders in lipoprotein metabolism, such as increased LDL-TGS and raised VLDL and LDL, result in the emergence of vascular compromise and subsequent occlusions.


Introduction
Retinal vein occlusion (RVO) has been recognised as a distinct entity and has been called "retinal apoplexy" by Leibreich in 1854 and "haemorrhagic retinitis" by Leber in 1877. [1] Retinal vein occlusion (RVO), a retinal vascular disease, is one of the most frequently occurring causes of visual loss worldwide. [1,2] It is the second occlusion were noted. A detailed history was taken, followed by a meticulous ocular and systemic examination and tailored lab investigations.

Statistical methods
The results were analysed using descriptive statistics and making comparisons between the groups Mg and NS. Discrete (categorical) data were summarized as in proportions and percentages (%) and quantitative data were summarized as mean ± SD. Statistical comparison was carried out using the Chi-square or Fisher's exact tests and independent t-test which were according to need. ANOVA test was used to analysed more than two group. The P < 0.05 will be considered statistically significant The following statistical methods were used for calculation and analysis in present study in the present analysis

Statistical tools employed
The statistical analysis was done using SPSS (Statistical Package for Social Sciences) Version 15.0 statistical Analysis Software. The values were represented in Number (%) and Mean±SD. The following Statistical formulas were used:

1.
Mean: To obtain the mean, the individual observations were first added together and then divided by the number of observations. The operation of adding together or summation is denoted by the sign .
The individual observation is denoted by the sign X, number of observations denoted by n, and the mean by X .

5.
Analysis of Variance: Analysis of Variance (ANOVA): The ANOVA test was used to compare the within group and between group variances amongst the study groups i.e., the three different sealers. Analysis of variance of these three sealers at a particular time interval revealed the differences amongst them. ANOVA provided "F" ratio, where a higher "F" value depicted a higher inter-group difference. Calculate an analysis of variance (e.g., One-way between-subjects ANOVA).

2.
Select two means and note the relevant variables (Means, Mean Square Within, and number per condition/group) 3.
Calculate Tukey's test for each mean comparison 4.
Check to see if Tukey's score is statistically significant with Tukey's probability/critical value table considering appropriate dfwithin and number of treatments. 7.
Paired "t" test: To compare the change in a parameter at two different time intervals paired "t" test was used.
where: dav is the mean difference, i.e., the sum of the differences of all the datapoints ( Table 3 and Figure 3 show the distribution of Retinal Vein Occlusion (RVO) according to gender. The percentage of male and female was 62% and 38% in cases and 54% and 46% in controls, respectively. The percentage of male and female was not significantly different in between groups.            Figure 7: Bar Chart shows the mean total cholesterol, TGS, HDL, LDL and VLDL in between cases and controls group. Table 8 and Figure 8 show the details of Maculopathy in cases and controls. The percentage of macular edema, macular edema+haemorrhage, macular edema+haemorrhage+exudates, macular exudates+macular edema+exudates, macular haemorrhage, R.D. and no maculopathy were 39.00%, 52.00%, 3.00%, 1.00%, 4.00%, 1.00%, 0.00% and 0.00% in cases and 6.0%, 1.0%, 9.0%, 0.00%, 1.0%, 0.00%, 0.00% and 83.0%, respectively. The distribution of different maculopathy was significantly different in between cases and controls.  Comparisons of Intraocular pressure (IOP) in cases and controls are shown in Table 9 and Figure 9. The mean OD and OS Intraocular pressure (IOP) was 16.08±7. 55 Table 11 and Figure 11 show the distribution of retinal vein occlusion (RVO) on the basis of occurring at different sites in cases. Out of 100, total 43% patients were branch RVO, 54% patients were Central RVO and 3% patients were hemi RVO.                  Figure 17: Bar chart shows the comparisons of Lipid Profile in between Branch, Central and Hemi RVO. Table 18 and Figure 18 show that the Maculopathy in Branch, Central and Hemi RVO. The different Maculopathy were not significantly different in between Branch, Central and Hemi RVO.    Table 20 and Figure 20.

Discussion:
The obstruction of veins that take blood away from the retina is known as retinal vein occlusion (RVO). As a result of macular edema and retinal ischemia, RVO-the second most prevalent retinal vascular disorder-is a reasonably frequent and common cause of vision loss, particularly in elderly people. Although it has been known about for more than a century, the precise pathophysiology is still unknown. Additionally, systemic diseases such as HTN, arteriosclerosis, diabetes, hyperlipidemia (HLD), vascular cerebral stroke, blood hyperviscosity, thrombophilia, inflammatory pathologies, neoplasia's, smoking, and oral contraceptives are linked to the risk of RVO. [25] In this study, we aim to evaluate the various risk factors and clinical presentation of retinal vein occlusion in patients visiting a tertiary eye care facility in Uttar Pradesh. A total of 200 people has signed up for this study.in which 100 patients (50%) had retinal vein occlusion (case group) and 100 patients (50%) were healthy (control group).in the study of 100 patients, 43% had branch RVO, 54% had central RVO, and 3% had hemi RVO. Bhattacharjee et al. (2020) [74] observed that 67.6% of the total patients had branch retinal vein occlusion (BRVO) and the remaining 32.4% had central retinal vein occlusion (CRVO). Laouri et al. [27] compared the data from one pooled analysis and seven population-based studies to assess the prevalence of RVO. According to this systematic review, the prevalence of rvo is relatively constant across all countries: in populations older than 40 years, it ranges from 0.3% to 2.1%, with highest values in Japan and Australia and lowest values in the United States, Europe, and Singapore. In all studies, the prevalence of BRVO was higher than that of CRVO, ranging from three (Singapore, 26) to 10 (China, 24) times higher. Data from Europe and the Rotterdam eye study were included in the pooled analysis. [75] In this pooled analysis, the prevalence of any RVO was 0.8% in Europe and 0.6% in the Rotterdam  [64] and Verougstraete (1999) [78] reported that age is an important risk factor for RVO. This likely reflects an increase in arteriosclerosis and in age-related vascular (e.g., systemic hypertension) and ocular (e.g., glaucoma or increased intraocular pressure) risk factors. [35,76] Barnett et al. (2010) [79] reported that the mean baseline age of participants who later developed RVO was 65.1 8.5 SD years, compared to 55.3 9.5 SD years among participants who did not develop RVO (p 0.001) . The pathogenic impact of various risk factors on both young and old people varies (Bucciarelli et al., 2017). [62] Ages 50-59 and 60-69 were found to have a greater risk of stroke in a metaanalysis by examining subgroups of various ages (Li et al., 2016). [77] Younger patients (50 years old) had superior baseline and final acuities, a reduced incidence of cystoid macular edema, and needed fewer intravitreal injections, according to a study (Thomas et al., 2019). [80] Less blood stasis and a more active lifestyle might probably contribute to the better patient outcomes seen in younger patients. On the other hand, natural ageing and organ wear would also have a negative impact on senior patients' prognoses. A greater risk of RVO may also be caused by other cardiovascular risk factors, such as increased lamina cribrosa thickness and hardness (where the retinal vein and artery vein are very close to one another) (Bucciarelli et al., 2017). [62] It is evident that CRVO is positively connected with age; hence, young patients with BRVO must be screened for thrombus causes (Ali et al., 2011). In our study, men were more frequently affected by RVO (62%  [53] reported that males were 1.7 times more frequently affected by RVO (prevalence of RVO in men: 0.52%) than females (0.29%). Rogers et al. (2010) [9] of these participants, 43 [81] showed that young CRVO occurrence was also found in women more than men, and young BRVO was noted in men more than women. However, these differences were not statistically significant. Another study, however, reported more cases in men than women and indicated that being male was one of the risk factors in the development of RVO (Fong et al., 1993). [82] Roger et al. (2004) [9] state that females were 25% less likely to have RVO than males. Ponto et al. (2014) found that males were 1.7 times more frequently affected by RVO (prevalence of RVO in men: 0.52%) than females (0.29%). RVO is more common in older adults and in males than in females (over 65 years of age). RVO prevalence data for the USA, Europe, Asia, and Australia were reported in a study by the International Eye Disease Consortium in 2010. [9] RVO prevalence for women increases from 55 to 84 years of age (Park et al., 2014). [47] This discovery could be connected to menopause and unhealthy lipid profiles (Pappa et al., 2012; Ko et al., 2021;Taddei et al., 2009). [83] RVO, on the other hand, affects men more frequently in people over 85 and between the ages of 30 and 54 (Park et al., 2014). [47] In our study, there was no significance noted in the laterality of the affected eye, as 37% had right eye involvement and 24% had left eye involvement. In our study, the best corrected visual acuity ( Mohamed et al. (1996) [85] stated that 48 percent of RVO is connected to hypertension. Sankaranarayanan et al. (2017) [86] reported that the associations of BRVO with uncontrolled hypertension were significantly higher (58%). Various previous studies reported that the BRVO was commonly associated with systemic hypertension. [86] Systemic hypertension occurs more frequently in the elderly population, which could be the reason for a higher prevalence of BRVO in our elderly population. Because our sample did not include CRVO estimates in the younger age group (60 years), where it is more common, we could have also underestimated the prevalence of CRVO. The population prevalence of CRVO was 0.21%. The finding was consistent with other studies where prevalence ranged from 0.1-0.4%. [41,68] The ARIC and CHS studies identified hypertension as one of the main risk factors for RVO, along with concomitant hypertensive retinal arteriolar alterations (such as the arteriovenous notch). BRVO is more affected by hypertension than CRVO is, and this difference is due to higher pressure at the point where the arteries and veins meet. Through pro-inflammatory processes of the renin-angiotensin-aldosterone system, hypertension results in RVO. Small arteries are also harmed, resulting in arteriolosclerosis and venule compression. This promotes turbulence, which slows the flow of venous blood. Additionally, the hematocrit is altered by hypertension, which damages the blood vessel walls, increasing blood viscosity and the likelihood of RVO. RVO and non-dipping hypertension were investigated by Rao et al. They discovered that the prevalence of non-dipping patterns was almost two times greater in RVO patients. [49] To strengthen the relationship even further, more research is required. Ninety-two percent of RVO patients who have hypertension have stable blood pressure. These hypertension studies indicate that dynamic blood pressure control and monitoring may reduce the risk of RVO.
The percentage of cases with diabetes in this study was significantly higher (32.0%) than in controls (13.0%). Moreover, the mean fasting, PP, and RBS blood sugars were 110.40±20. 82 ,768,820 controls, which supported the finding that individuals with DM were positively related to an increased risk of RVO. [87] Furthermore, they discovered no link between diabetes and the risk of BRVO, but diabetes was a risk factor for the CRVO and mix groups. Previously, Pinna et al. [88] found that the prevalence rate of DM was lower in the BRVO group (12.2%) than in the control group (15%). However, Demir et al. [89] and Christodoulou et al. [90] indicated that the prevalence rate of DM was higher in the BRVO group (24% and 16.7%, respectively) than in the control group (14% and 2.4%, respectively). Santiago et al. (2014) [91] reported that the prevalence of CRVO in diabetic patients (N = 72 27) were 0.5 and 0.4%, respectively. Disc neovascularization (21.3 vs. 0.0%, P = 0.05) was more common in diabetic patients compared with nondiabetic patients. Compared with type 2 diabetic patients, retinal neovascularization (28.6 vs. 3.7%, P = 0.004) and subsequent PRP (78.6 vs. 41.9%, P = 0.01) were more likely in type 1 diabetic patients. Optic nerve head collateral vessels (CVs) were observed less than half as often (21.4 vs. 56.5%, P = 0.04) in patients with type 1 diabetes. End products of advanced glycosylation can accumulate excessively in response to persistently high glucose levels, altering the function of the extracellular matrix, basement membrane, and vascular wall structure. End-stage diabetes mellitus changes could be crucial for BRVO. According to a recent study, sodium-glucose cotransporter 2 (SGLT2) inhibitors increased the incidence of RVO because they changed the blood's composition. Adipo, which modifies obesity and diabetes, raises CRVO. According to a study, the severity of DM affects the link between body mass index (BMI) and RVO. The link between BMI and RVO may be explained by the hormone adipo.
In this study the mean total Cholesterol, TGS, HDL, LDL and VLDL were 178.54±19. 87 [92] reported that the comparison to controls, patients with RVO and RAO exhibited significantly higher LDL cholesterol levels (3.82+/-1.06, 3.59+/-0.90, and 3.07+/-0.83 mmol/L), LDL triglyceride levels (0.39+/-0.14, 0.40+/-0.12 and 0.35+/-0.14 mmol/L), and apolipoprotein B levels (1.06+/-0.27, 1.05+/-0.26 LDLtriglycerides and retinal vascular occlusion in RAO were independently correlated. According to the current investigation, Dodson and colleagues found a tendency toward higher HDL-C levels in retinal vein occlusion. [93] HDL may not defend against the obstruction of retinal veins for unknown reasons, although it may be due to unique qualities of the retina's vascular bead that set it apart from other bodily vessels. It was also surprise that our patient groups had a tendency toward reduced VLDL concentrations, which was especially significant in the case of RVO. This conclusion is feasible, though. The concentration of VLDL and HDL have a strong inverse biochemical and statistical relationship, thus the low VLDL found in the current study may only be a reflection of the high HDL (or vice versa). An antiatherogenic lipoprotein called HDL inhibits the transfer of cholesterol in the reverse direction, which has positive vascular and antithrombotic benefits. 18 Additionally, the total cholesterol, HDL, or LDL/HDL atherogenic indexes, as well as other non-HDL cholesterol levels, were significantly higher in our RVO patients. These ratios combine two potent components of vascular risk, and subjects with elevated ratios have a higher cardiovascular risk due to a greater imbalance between the cholesterol transported by the most atherogenic lipoproteins and that of the lipoproteins with a protective effect. These indices represent risk markers with a higher predictive value than that of isolated data. The majority of our patients with RVO are categorized into the moderate-risk lipid intervals (LDL 40/50 (men and women)). A triglyceride study of a national cohort stated there was an association between low HDL levels and the risk of developing an RVO. However, as reported by Oriole et al., when analyzing the anterior lipid profile of a vascular event, the parameters are not overly high. According to Newman-Casey et al., elevated serum triglyceride levels and a decline in HDL levels were both risk factors for the development of peripheral RVO. A frequent risk factor, particularly in people under 50, is hyperlipidemia. Hyperlipidemia affects roughly 20.1% of people (Park et al., 2015). [47] Hyperlipidemia and RVO may be related to alterations in platelet function, clotting improvement, and plasma viscosity. The activity of plasminogen activator inhibitor type 1 (PAI-1) is increased in people with hyperlipidemia. Another independent risk factor for RVO is PAI-1. Further investigation reveals a connection between RVO and the genotype of PAI-1 4G. This offers a fresh approach to treating thrombotic RVO. RVO has also been connected to cigarette smoking. HTN Barnett et al. (2010), CRVO/HRVO had a cumulative incidence of 1.3%, which was more than four times higher than BRVO's incidence of 0.3%. This is in stark contrast to the Beaver Dam Eye Study's 5-year data, which showed the ratio to be 0.6% for BRVO and 0.2% for CRVO (HRVO was not identified separately). Similar to the Blue Mountains Eye Study, 1.2% BRVO and 0.4% CRVO were the incidence rates of BRVO over a 10-year period (including HRVO). The reversal of the ratio of BRVO to CRVO/HRVO in the OHTS versus previous population-based studies may be connected to the necessity for elevated IOP for inclusion in the OHTS, given the stronger association between elevated IOP and CRVO/HRVO documented in the literature. The percentages of macular edema, macular edoema + hemorrhage, macular exudates + macular edoema + exudates, macular exudates + macular edoema + exudates, macular haemorrhage, R.D., and no maculopathy in this study were 39.00%, 52.00%, 3.00%, 1.00%, 4.00%, 1.00%, 0.00%, The distribution of different maculopathies was significantly different between cases and controls. Moreover, the different maculopathies were not significantly different between the branch, central, and hemi RVOs. Strokes are a frequent risk factor for CRVO (51), and they are 45% more likely to occur in people with RVO. Furthermore, the risk of hemorrhagic stroke rose 30 days after the start of RVO. Chen and co. (2018) RVO patients are much more likely to experience hemorrhagic, ischemic, and stroke events. The probability of having an ischemic or hemorrhagic stroke was considerably higher in RVO patients than in non-RVO individuals. It makes more sense to assess ischemic stroke and hemorrhagic stroke separately since thrombosis in RVO may be more closely linked to the development of thrombosis or emboli in ischemic stroke. Hemorrhagic and ischemic strokes were separately assessed in only one prior study. In that study, RVO considerably raised the risk of ischemic stroke, according to Rim

Conclusion:
The present study was carried out to evaluate the various risk factors and clinical presentation in retinal vein occlusion patients visiting a tertiary care eye hospital in Northern Uttar Pradesh. For this purpose, a casecontrol study was carried out that included a total of 200 individuals. In this study, 100 patients (50%) had retinal vein occlusion (case group) and 100 patients (50%) were healthy (age-matched control group).
In the general adult population aged 40 and up, we found that 43% of patients had BRVO, 54% had CRVO, and 3% had hemi-RVO. The males were more frequently affected by RVO. Diabetes and hypertension were significantly more common in RVO patients. Our findings imply that dyslipidaemia plays a major role in the aetiology of disorders of the retinal vascular system. Disorders in lipoprotein metabolism, such as increased LDL-TGS and raised VLDL and LDL, result in the emergence of vascular compromise and subsequent occlusions. Hence, dyslipidaemia is an important modifiable etiological factor while treating patients with RVO. The following conclusions were drawn from the study: This study enumerates the etiological factors contributing to visual loss in patients with RVO. A scientific approach is warranted to treat these factors to achieve better therapeutic results in patients with retinal vascular occlusion.
In our population, retinal vein occlusion is a common retinal vascular disorder in the elderly. The BRVO is more common than the CRVO. The main risk factors for RVO were increasing age, male gender, diabetes, and hypertension. Moreover, diabetes was also significantly more common in RVO patients as compared to controls. The lipid profile was also one of the significant risk factors for RVO. Regular eye examinations in the high-risk group coupled with timely detection and treatment of retinal vascular occlusions could help prevent blindness in this elderly population. While eyes with poor beginning acuity show a poor visual outcome, eyes with good initial vision have a better chance of sustaining exceptional vision. RVO can be prevented from recurring with early recognition and effective control of relationships. For the prevention and treatment of sequelae, patients with RVO require routine follow-up.