research in practice

Systemic
Correlations - Part1

New links between anterior segment and systemic conditions

Mile Brujic, O.D.,
Crystal Brimer, O.D.

Recent studies establish new correlations between ocular and systemic conditions. These studies will assist us in diagnosing and treating these conditions early, enhancing our patients' lives.

In part one of this two-part series, we discuss research on the associations between anterior segment and systemic conditions.

Supporting research

The recent studies:

1. Keratoconus and sleep apnea. One study reveals keratoconus (K) patients have a higher incidence of obstructive sleep apnea (OSA) vs. that accepted for the general population (4%).¹ Specifically, a total of 18% of 101 K patients presented with the OSA diagnosis. Of the remaining 83 patients (those without the diagnosis), the researchers determined 47% were at high risk for developing the condition based on the Berlin Questionnaire (a sleep apnea screening tool).

Here are two slit lamp images of a 62-year-old male keratoconic patient who appeared overweight and was diagnosed as having obstructive sleep apnea.

The study's researchers enrolled 101 K patients randomly chosen from an eye center. They then asked those who did not present with the OSA diagnosis to complete the Berlin Questionnaire. The researchers then performed a statistical analysis to determine OSA prevalence and compare it with the general population's previously reported prevalence data.

Another study shows that of 92 K patients, 18, or 19.6%, presented with the sleep apnea diagnosis, while six, or 6.5%, of the control patients (also 92) presented with the diagnosis.² Furthermore, the researchers deemed 49, or 53.3%, of the K patients at high risk for the condition based on the Berlin Questionnaire, vs. 25, or 27.2%, of the control patients. Of interest: In K patients, body mass index (BMI) was the only sleep apnea risk factor, while age, BMI and sleep apnea family history were the risk factors for the condition in the control patients.

The study's researchers used logistic regression to study the risk factors linked with a high risk of sleep apnea in K patients and in the control group.

2. Pinguecula and diabetes. One study reveals diabetes mellitus (DM) may be associated with pinguecula development.³ Specifically, after correcting for patient age, the DM group had both a higher incidence and severity of pinguecula of both the nasal (55% vs. 40%) and temporal (54.4% vs. 40%) conjunctiva vs. the control group.

The study's researchers enrolled 160 type 2 diabetes patients age 31 to 70 in the DM group and 160 controls age 31 to 70. They then assessed the nasal and temporal pinguecula grade in all subjects.

3. Dry eye disease (DED) and depression. One study shows depression is a risk factor for DED symptoms in elderly subjects who have normal or near-normal tear production, as determined by a Schirmer score of >5mm.⁴

The study's researchers enrolled 657 patients between age 65 and 95 they randomly selected. They assessed both depression and dry eye symptoms based on the Short Geriatric Depression Scale and a six-item Dry Eye Questionnaire, respectively. Also, the researchers acquired Schirmer scores, fluoresceinstaining scores and tear breakup time (TBUT) values to determine DED sign clinical severity and they performed a linear analysis.

Implications for patient care

The patient care implications:

1. Keratoconus and sleep apnea. Because sleep apnea is shown as a stand-alone risk factor for cere-brovascular disease, cardiovascular disease, a reduced life expectancy and even death, it's imperative we're aware of this link, so we can recommend sleep study analysis to K patients who present sans the OSA diagnosis and have a high BMI. Incorporating this practice can have a significant influence on both the quality and length of their life. Further, this correlation shows it's worthwhile to examine the corneal shape of our patients who present with the sleep apnea diagnosis though not the K diagnosis.

A caveat: Continuous Positive Airflow Pressure (CPAP) masks are a common sleep apnea treatment, but can be harmful to both lid structure and ocular surface integrity.⁵ Specifically, the lids may show an upper ptosis, lower lid ectropium, blepharochalasis, or trichiasis. Corneal findings: infectious K, dry eye, recurrent erosion, K and progressive endotheliopathy.⁵

Also, a CPAP and the ocular surface study shows a post-treatment increase in ocular irritation, tear evaporation and conjunctival squamous metaplasia.⁶ So, we must follow CPAP patients closely. CPAP patients with extreme ocular compromise might benefit from utilizing a different mask design.

The study's researchers conducted surface staining, Schirmer testing, TBUT, slit lamp evaluation and conjunctival impression cytology on 80 eyes of 40 patients before CPAP therapy and after four months of treatment.

2. Pinguecula and diabetes. In recognizing this connection, we must consistently remind our diabetic patients of the importance of wearing UV eyewear. Further, considering pinguecula's aesthetic consequence, providing patient education about this link may promote patient compliance to sunwear.

3. Dry eye disease (DED) and depression. Realizing this correlation, we must consider the many explanations.⁴ To start, the contributing etiology and secondary effects of the two conditions overlap to some degree. Sex hormones likely play a role in both, as being female and menopausal are risk factors for depression and DED. There may also be common omega 3 links in the disease mechanisms, as omega 3 is shown an effective DED treatment, and researchers have found reduced levels of omega 3 in depression patients. Consider this: Depression can induce elevated cytokine production, which increases inflammation and can worsen the DED. And patients with depression may have a lower threshold for pain. Up to 80% of depressed individuals experience various symptoms without a discernable cause.⁷ And, of course, if a patient is aggravated by the visual and painful effects of dry eye, it can advance their depression.

The bottom line: Understanding more about the complex association between depression and DED can help us better educate our patients and potentially open a discussion for the possible presence of depression in undiagnosed individuals. Considering the devastation advanced depression can have on one's life, the potential to diagnose it sooner is of great value.

Previous correlations between ocular and systemic diseases have not only enabled us to play a vital role in our patients' health, but also become recognized as an essential part of the healthcare team. Knowledge of these new links will likewise allow us to enhance patient care. OM

In Part two, we'll discuss the links between posterior segment and systemic conditions.

1. Gupta PK, Stinnett SS, Carlson AN. Prevalence of sleep apnea in patients with keratoconus. Cornea. 2012 June;31(6):595-9.
2. Saidel MA, Paik JY, Garcia C, et al. Prevalence of sleep apnea syndrome and high-risk characteristics among keratoconus patients. Cornea. 2012 June;31(6):600-3.
3. Mimura T, Obata H, Usui T, et al. Pinguecula and diabetes mellitus. Cornea. 2012 Mar;31(3): 264-8.
4. Kim KW, Han SB, Han ER, et al. Association between depression and dry eye disease in an elderly population. Invest Ophthalmol Vis Sci. 2011 Oct 10;52(11):7954-8.
5. Mojon D. Eye diseases in sleep apnea syndrome. Ther Umsch. 2001 Jan;58(1):57-60.
6. Hayirci E, Yagci A, Palamar M, et al. The effect of continuous positive airway pressure treatment for obstructive sleep apnea syndrome on the ocular surface. Cornea. 2012 June;31(6):604-8.
7. Hamilton M. Frequency of symptoms in melancholia (depressive illness). Br J Psychiatry. 1989 Feb;154:201-6.