To the Editor:
The article “Lid Laxity: Diagnosis and Management” in the Plastics Pointers department of the February issue of Review of Ophthalmology (pp. 46-48) was of great interest. The importance of correlating eye diseases with medical conditions (e.g., obstructive sleep apnea, or OSA) has therapeutic implications for patients and genetic implications for families. 

In addition to OSA, other medical conditions have been associated with Lax Eyelid Syndrome. In 1984, LES was reported in a patient with non-ketotic hyperglycemia.1 The case was of particular interest since glycine is a major constituent of collagen. This biochemical defect probably led to weaker collagen fibers and thus greater susceptibility to physical trauma (explaining the association of LES with sleeping on one side). This patient’s brother also had non-ketotic hyperglycemia, and the genetic defect was subsequently identified in the brother.2 In the era of gene therapy it will be possible to correct the genetic defect, thus eliminating many problems!

Edward W. Gerner, MD

1. Gerner EW, Hughes SM. Flopped eyelid with hyperglycemia.  Am J Ophthalmology 1984:98;614-616.
2. Baker PR II, et al. Variant non-ketotic hyperglycemia is caused by mutations in LIAS, BOLA 3 and the novel gene GLRY5. Brain 2014:137;266-379.


Dr. Armstrong responds:
Thank you for your thoughtful letter. 

In addition to obstructive sleep apnea, there are a variety of genetic conditions that have been described in association with lax eyelid syndrome, including Down syndrome, congenital cataracts facial dysmorphism neuropathy (CCFDN), and congenital hyperglycinemia.1-3 LES also presents in patients with Ehlers-Danlos syndrome with mutations in the COL5A1 and COL5A2 genes coding for type V collagen.4 

These varied heritable conditions are unified in that the individual genetic mutation compromises the integrity of the tarsal connective tissue and causes eyelid laxity. When lid laxity reaches a critical threshold—or perhaps is exacerbated by mechanical trauma—the inflammatory sequelae of the conjunctiva and ocular surface result. The genetic associations can elucidate the pathogenesis of LES and, as you suggest, in this exciting era of gene therapy may offer a potential for future treatment. 


1. Fowler A, Dutton J. Floppy eyelid syndrome as a subset of lax eyelid conditions: Relationships and clinical relevance. Ophthal Plastic Reconstructive Surg 2010;26:3:195-204.

2. Rao L, Bhandary S, Devi A (2006). Floppy Eyelid Syndrome in an Infant. Indian Journal of Ophthalmology 2006;54:3:217-8.

3. Eiferman R, Gossman MD, O’Neill K, Douglas CH. Floppy Eyelid Syndrome in a Child. Ophthalmic Plastic and Reconstructive Surgery 1991;109:3:74-75.

4. Segev F, Heon E, Cole W, Wenstrup R, Young F, et al. Structural abnormalities of the cornea and lid resulting from collagen V mutations. IOVS 2006;47:2:565-573.