Androgenic Rescue of Meibomian Glands? By Julio Echegoyen md, PhD



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Androgenic Rescue of Meibomian Glands?
By Julio Echegoyen MD, PhD.

Gavin Herbert Eye Institute, University of California Irvine

Irvine, CA.

History
A 79-year-old male was referred to the Gavin Herbert Eye Institute for evaluation of dry eyes. He initially noticed his symptoms 3 months ago after having surgery for an abdominal aortic aneurysm. Immediately after his surgery, he developed significant epiphora and photophobia. He had been unsuccessfully treated for dry eyes with a regiment of preservative free artificial tears (PFAT) and prednisolone acetate by his previous ophthalmologist without improvement of symptoms. His past medical history included osteoarthritis, depression and hypothyroidism. His past ocular history was unremarkable except for bilateral cataract surgery six years ago.

At the time of referral, he was still experiencing significant symptoms of irritation and photophobia, which were subjectively affecting his quality of life.


Examination
On initial presentation, examination revealed an uncorrected visual acuity of 20/20 -2 OD and 20/25 OS. Biomicroscopy of the anterior segment demonstrated 2-3+ posterior blepharitis with Meibomian Gland Dysfunction (MGD). Tear break up time (TBUT) was determined to be 3-5 seconds (normal >10 seconds). The conjunctiva appeared white and quite. Fluorescein staining of the corneal surface revealed 1+ superficial punctual keratopathy (SPK), and, although lissamine staining would have more completely evaluated the ocular surface, this stain was not available on our initial exam. The iris and pupil were unremarkable and the patient was pseudophakic bilaterally. A dilated fundus exam was within normal limits.
Discussion and diagnosis

MGD is a common condition believed to be one of the leading causes of evaporative dry eye1, perhaps affecting millions of individuals. The etiology of MGD is likely multifactorial. However, dysfunction of the meibomian glands may involve inflammatory processes, abnormal production of and hypo/hypersecretion of meibum (the excretions produced by meibomian glands)2. MGD ultimately results in poor tear film quality and instability leading to increased evaporation and ultimately, dry eye.

Treatments for MGD aim to improve the flow and quality of meibum and initially include the use of warm compresses and lid hygiene. For more severe cases, oral antibiotic therapy (particularly doxycyline or other tetracyclines) may be implemented with or without antibiotic ointment lid scrubs.

At his initial visit, the patient was started on a regimen of warm compresses/lid hygiene and oral doxycycline (50 mg, twice a day) for MGD. He also continued PFAT therapy. A return visit two weeks later showed no improvement of either clinical findings or subjective symptoms. Over the next three months, additional interventions included initiation of lotoprednol and cyclosporine therapy, placement of punctal plugs bilaterally, and one treatment with the Lipiflow® system (TearScience, Inc., Morrisville, NC). Together, these interventions mildly improved his symptoms. His clinical findings however, continued to show 2-3 + MGD (of note, the quality and flow of the meibum was observed to improve after Lipiflow® treatment).

Interestingly, our patient revealed that he had started topical testosterone gel therapy (applied to the underarm skin), for low testosterorne levels, around the time of his Lipiflow® treatment. Two months after starting topical testosterone treatment, both the quality of meibum and clinical score of his MGD began to dramatically improve (previously 2-3+ to 1-2+ over 4 months). In addition, TBUT slowly improved to a normal time of 17 seconds. His subjective symptoms improved significantly.

Although Lipiflow® is know to improve meibomian gland secretion and TBUT3, the influence of androgens on meibomian glands has also been reported4.

Lipiflow® is a novel and effective treatment for MGD5, and indeed, a single treatment has been reported to improve MGD for up to 9 months3. Nonetheless, after observing the dramatically improved clinical presentation in our patient, we were intrigued by the potential influence that topical androgen therapy may have on MGD.

Androgen influence on meibomian glands has been previously demonstrated in both animal models6 and human subjects taking anti-androgen therapy7. In animal models, androgens have been shown to influence many aspects of meibomian gland function, including gene expression and lipid production6,8. In humans, anti-androgen therapy also results in alteration of the meibum lipid profile7. To date, no studies have determined the specific role of physiological decreases in androgens (as seen in ageing men) or whether they result in increases in MGD.


Conclusions

It is now well established that MGD is a significant cause of evaporative dry eye, and that more attention must be placed in early detection and treatment9. As a multi-factorial disease, MGD will most likely require a tailored combination of therapeutic strategies. One potential approach in ageing men may involve Testosterone replacement therapy. As described earlier, androgens have profound influences on meibomian glands, and, at least experimentally7, androgen replacement therapy may restore meibomian gland function. Further studies are needed to help elucidate the effect of androgen deficiency in the ageing male (and possibly female) population. As our aging population increases, the number of individuals suffering from MGD will increase. Unfortunately, clinical signs of MGD are often brushed aside; and patients may forego early therapy. Given the influence that androgens have on meibomian gland physiology and with the availability of topical androgen replacement therapies, androgen replacement may have potential in augmenting meibomian gland secretion in select patients suffering from MGD.


References

1 Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, Lemp MA, and Sullivan DA. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. IOVS, Special Issue 2011, Vol. 52, No. 4; 1922-1929.


2 Knop E, Knop N, Millar T, Obata H, and Sullivan DA.The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland. IOVS, Special Issue 2011, Vol. 52, No. 4; 1938-1978.
3 Greiner JV. A Single LipiFlow® Thermal Pulsation System Treatment Improves Meibomian Gland Function and Reduces Dry Eye Symptoms for 9 Months

Current Eye Research, 2012, Vol. 37, No. 4; 272-278.


4 Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagachi, H, Liu M, Richards SM, Suzuki, T, Schaumberg DM, SULLIVAN RM, and Reza Dan AM Androgen Deficiency, Meibomian Gland Dysfunction, and Evaporative Dry Eye. Ann. N.Y. Acad. Sci. 2002. Vol 966: 211–222.
5 Lane SS, DuBiner HB, Epstein RJ, Ernest PH, Greiner JV , Hardten DR, Holland EJ, Lemp MA MD, McDonald II, JE MD, Silbert DI, Blackie CA, OD, Stevens CA, and Bedi, R. A New System, the LipiFlow, for the Treatment of Meibomian Gland Dysfunction. Cornea 2012, Vol 31; No 4; 396-404.
6 Schirra F, Suzuki T, Richards SM, Jensen RV, Liu M, Lombardi MJ, Rowley P, Treister NS and Sullivan DA. Androgen Control of Gene Expression in the Mouse Meibomian Gland, IVOS, 2005, Vol 46, No. 10; 3666-3675.
7 Krenzer KL, M. Dana R, Ullman MD, Cermak JM, Tolls DB, Evans JE and Sullivan DA.Effect of Androgen Deficiency on the Human Meibomian Gland and Ocular Surface.

J Clin Endocrinol Metab, 2000, Vol. 85: 4874-4882.


8 Sullivan DA, Sullivan BD, Ullman MD, et al. Androgen influence on the meibomian gland. IVOS. 2000; Vol. 41; 3732– 3742.
9. Foulks GN, Nichols KK, Bron AJ, Holland EJ, McDonald, Nelson JD, Improving Awareness, Identification, and Management of Meibomian Gland Dysfunction. . Ophthalmology, Vol 119, No 10, Supplement, October 2012; S1-S12.


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