Age-related macular degeneration (AMD) is a disease of the retina in the elderly which can lead to irreversible blindness & is characterized by drusen, pigmentary changes, choroidal neovascularization, & geographic atrophy. While AMD is one of the leading causes of visual impairment worldwide & increasing in prevalence [1], the exact pathophysiology & pathways leading to AMD are not entirely understood. Thyroid hormones are known to regulate various visual functions in experimental & human studies [2]. Human retinal pigment epithelial (RPE) cells express thyroid hormone receptors & seem to be a direct target for thyroid hormones [3]. Recently it was shown that suppression of thyroid hormone signaling resulted in preservation of cone photoreceptors in mouse models of retinal degeneration [4]. In contrast, administration of active thyroid hormone leads to deterioration of cones. Thyroid dysfunction & subclinical thyroid dysfunction are common in the general population, with a prevalence up to 10%. These thyroid disorders are associated with various cardiovascular risk factors, including alterations in lipid levels, atherosclerosis, & hypertension [5], which are known predisposing factors for development & progression of AMD [6]. However, there are no studies in the general population assessing the association between thyroid function & the risk of AMD.

Age-related macular degeneration (AMD) is a prevalent disease leading to blindness & involves the loss of a person’s central field of vision. Globally, the prevalence of AMD, which is the leading cause of irreversible loss of vision among elderly individuals, is expected to increase with population aging, ranking third as a cause of blindness after cataract & glaucoma [7]. AMD is a complex multifactorial disease accounting for 8.7% of cases of blindness worldwide, & its prevalence is increasing & spreading. The global population is expected to grow to approximately 9.5 billion by 2050, &  it was estimated that there were nearly 2.4 billion people ≥60 years in 2050[8].

Thyroid function measures were taken only from Amaltas Institute of Medical Science, Dewas for 06 months. Participants who presented with normal TSH levels (0.1–4.0 mIU/L) did not have serum FT4 measured. Participants had serum FT4 measures available regardless of whether serum TSH levels were in the normal range or not. The main analysis presented in this paper is on the association between thyroid function status & incidence of AMD; however, we also present analysis of data on thyroid function status &             incidence of AMD data, primarily to establish the associations of serum FT4 in the full range with risk of AMD.

The detailed methodology of assessing for the presence of AMD has been previously reported. Briefly, we took two stereoscopic color retinal photographs of the macula of both eyes, which were graded AMD by experienced graders.

The inclusion criteria:

1. evaluated the association between thyroid medication or thyroid function & AMD risk;
2. performed with human subjects;
3. had adequate data for extraction or calculation, which may be presented as the odds ratio (OR) or relative risk (RR) & 95% confidence interval (CI).

The exclusion criteria:

1. duplicate articles

2. articles with incomplete data

Table No. 1: Baseline Profile of cases

Age Mean 64.9±3.9

Table No. 2: Smoking & Hypertension

Table No. 3: Thyroid status

Hypothyroidism & hyperthyroidism were associated with an increased risk for the development of exudative AMD. Significantly associated (p<0.05)

Table No. 4: Baseline Quintiles of Serum FT4 Levels

There was no significant association between increasing quintiles of serum FT4 levels

Age-related macular degeneration (AMD) is a prevalent disease leading to blindness & involves the loss of a person’s central field of vision. Globally, the prevalence of AMD, which is the leading cause of irreversible loss of vision among elderly individuals, is expected to increase with population aging, ranking third as a cause of blindness after cataract & glaucoma [9].

In this prospective cohort study we investigated the association between thyroid function & incidence of AMD. Higher FT4 values were associated with an increased risk of developing AMD, even within the normal range of TSH & FT4, while there was no association between TSH & AMD. The similar findings between higher FT4 levels & retinal pigment alterations might suggest that thyroid hormone plays a role in the development of AMD rather than just acting as a promoter of disease[10]. To our knowledge, this is the first prospective population-based cohort study to look at the association between thyroid function & AMD.

A limited number of studies investigating thyroid disease & AMD have been published, all lacking laboratory assessment of thyroid function. Bromfield et al. reported an increased risk of AMD in subjects with selfreported hypothyroidism [11]. A case–control study by Anand et al. reported an association between thyroid hormone use & a higher risk of AMD with geographic atrophy, but no data were reported on the number of patients that were over- or undertreated. Similarly, the Beaver Dam Eye study also reported an association between thyroid hormone use & early AMD, but this was not confirmed by Douglas et al. [12]. As mentioned previously, none of these studies had laboratory assessment of thyroid function nor did they investigate the association in a time-to-event analysis. In our study, excluding all subjects using thyroid medication did not alter risk estimates, supporting a potential intrinsic effect of thyroid hormone.

Thyroid dysfunction has been linked to cardiovascular risk factors & disease, including effects on the vascular function, lipids, & atherosclerosis [13]. As some of these risk factors are also linked to AMD, one could speculate about a joint vascular pathway leading to both thyroid dysfunction & AMD or perhaps that the relation between thyroid dysfunction & AMD could be mediated through this pathway. We were not able to confirm these hypotheses. First of all, these cardiovascular risk factors are mainly seen in hypothyroidism, (high TSH & low FT4), whereas our data show an association between high FT4 & AMD[14]. Also, correcting for some of these risk factors (for example, hypertension) that could act as confounders & possible mediators did not change risk estimates, suggesting that the effect of thyroid function is not through these pathways. Lastly, the VEGF-A gene was found to be significant in the look-up for the TSH GWAS & not the FT4 GWAS.

AMD is a disease whose risk factors & pathophysiology are not well understood; thus AMD is often diagnosed in an already advanced stage. Thyroid hormones may contribute to a better characterization of AMD in clinical practice. Even though observational studies cannot determine causal inference, they provide useful evidence to improve the perception of specific illnesses, understand better the role of thyroid hormones in the pathogenesis of the AMD disease.

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