Advertisement

PentaVision

Corneal Physician

Article

Treating Conjunctivochalasis

The basis for treating this common, but misunderstood and underdiagnosed, cause of tear film instability

By: NEEL R. DESAI, MD
Corneal Physician April 1, 2020 Vol 24, Issue April 2020 Page(s): 36-38, 40

Conjunctivochalasis (CCH) describes the complex of Tenon’s degeneration, conjunctival laxity, orbital fat prolapse, fornix foreshortening, and an obliterated tear reservoir and meniscus. It is a leading cause of tear film instability, visual disturbance and ocular discomfort in the aging population.1

The ideal treatments for CCH should produce improvements in both physical and visual symptoms quickly and for the long term. First and foremost, successful treatment should help to restore the normal anatomy and physiology to the bulbar conjunctiva and inferior cul-de-sac to facilitate restoration of the normal precorneal tear film dynamics within the meniscus and tear reservoir. Second, treatment should resolve the deficiency of healthy conjunctiva and Tenon’s capsule and provide some mechanism for conjunctival/Tenon’s replacement with improved functional tissue characteristics. An ideal approach should also address the prolapse of orbital fat and foreshortening of the inferior cul-de-sac, while improving tear retention, tear quality, and response to topical therapies. Above all else, successful treatment strategies for CCH should not risk exacerbation of any aspect of underlying pathophysiology, especially ocular surface inflammation.

An accurate understanding of the pathophysiology underlying this form of mechanical dry eye is foundational in choosing amongst treatments (Figure 1).

   
FIGURE 1. Note the prolonged retention of fluorescein long after instillation, due to delayed tear clearance and variability or feathering of the tear meniscus from canthus to punctum in these mechanical dry eye patients. (A) Restored uniformity of tear meniscus after preserved amniotic membrane use. (B).
FIGURE 1. Note the prolonged retention of fluorescein long after instillation, due to delayed tear clearance and variability or feathering of the tear meniscus from canthus to punctum in these mechanical dry eye patients. (A) Restored uniformity of tear meniscus after preserved amniotic membrane use. (B).

Aging and cellular senescence, in the form of increased expression of senescence-associated genes, activated by MMP-9 and seen in other forms of ocular surface disease, seem to have a strong relationship with the development of CCH.2 (Table 1). Inflammation and oxidative stress also play a key role in pathogenesis, as CCH fibroblasts show increased expression of MMP-1 and MMP-3.3

Despite ample evidence of an inflammatory etiology, histopathological study fails to find a significant difference between the conjunctiva of eyes with and without CCH. It has been proposed that delayed tear clearance results in accumulation of inflammatory mediators in the subconjunctival connective tissues, resulting in elastotic degeneration and collagenolysis of Tenon’s.4 Resulting conjunctival laxity, rather than any excess, then allows orbital fat prolapse, which further foreshortens the tear fornix. Furthermore, intraoperative surgical observation of degenerated or absent Tenon’s capsule during CCH surgery spurs speculation that the locus of primary disease in conjunctivochalasis, despite nomenclature, is not the conjunctiva itself, but the underlying Tenon’s capsule. In short, this may not be a primary disease of the conjunctiva at all, but rather a destructive inflammatory process in the underlying Tenon’s capsule.

Treatment approaches to CCH are as varied as the signs and symptoms of the disease they aim to treat — ranging from topical medical therapy to evolving surgical procedures. These approaches are described below.

Topical Therapies

Because CCH is often accompanied by aqueous tear deficiency and meibomian gland dysfunction, topical therapies, such as artificial tears, ointments, and autologous serum drops, remain a mainstay treatment. The use of topical corticosteroids to break the inflammatory cycle can also be helpful.5

Conjunctival Cauterization

Cauterization of bulbar conjunctival folds has been used to attain contracture and scarring of bulbar conjunctival folds in an effort to reduce “redundancy” and poor adherence.6,7 Variations upon cauterization techniques, from direct electrothermal cautery via an argon green laser, have produced at least short-term improvement in some ocular signs and symptoms without sacrificing conjunctival tissue, the use of sutures, or prolonged operative times.8 It may be difficult to gauge how much conjunctiva to cauterize and to what extent, so repeat treatments may be necessary.9 Early complications may include foreign body sensation, pain, hyperemia, chemosis, subconjunctival hemorrhage, and visible cicatrization of the bulbar conjunctiva. It is unknown how cauterization may impact, long term, the degree of conjunctival inflammation, scarring, and contraction, fornix foreshortening, orbital fat prolapse, or conjunctival epithelial phenotype (i.e. goblet cell density).

Excision of Conjunctiva

Excision techniques have success rates ranging from 84.8% to 93.3% in producing improvements in tear break-up time, staining scores, and tear film stability.10 Several such techniques involving primary excision of inferior bulbar conjunctiva, in amounts varying in area from 5 mm-10 mm by 25 mm, with direct closure with suture or tissue glue have been described.11-14

Suture closure can incite an inflammatory reaction, pyogenic granuloma, suture abscess, pain, and increased surgical time. To avoid suture-related complications, several techniques utilizing fibrin glue have been developed. For example, the “paste-pinch-cut” technique is comprised of first injecting fibrin glue into the inferior bulbar subconjunctival space and grasping loose conjunctiva while the glue coagulates, and then excising the folded “excess.”

All techniques involving simple conjunctival resection carry the risk of potential exacerbation of inflammation, foreshortening of the inferior fornix, restricted motility, visible scarring, and prolonged healing if the surgeon is overzealous in the amount of conjunctiva resected.3 Furthermore, excised conjunctiva does not regenerate. This may produce further deficiency in goblet cell density and worsen dry eye syndrome throughout the long term, or could complicate future transconjunctival surgery or glaucoma-filtering procedures.

Cryopreserved Amniotic Membrane

This may impart key structural and biologic benefits, while preserving surgical efficiency. Active biological factors within a cryopreserved amniotic membrane are known to promote re-epithelialization and healing, while simultaneously preventing scarring via the suppression of proinflammatory matrix metalloproteases (MMPs) and cytokines, such as tumor necrosis factor (TNF-α), transforming growth factor (TGF-β), and fibroblast growth factor (FGF).15-17 Furthermore, the active biologics delivered via the membrane, most notably high molecular weight complexes (HC-HA) and Pentraxin-3, appear to facilitate regeneration and restoration of other key physiologic and phenotypic features of the ocular surface. Specifically, these biologics are shown to support the proliferation of conjunctival epithelial cells and significantly increase differentiation of goblet cells by nearly 10-fold in the newly regenerated conjunctiva.18-20 In patients with commonly overlapping features of CCH and ocular surface disease due to dry eye syndrome, wherein there may be a loss of normal goblet cell density and, consequently, a relative mucin deficiency, this effect may be of particular benefit.

Additionally, a cryopreserved amniotic membrane appears to facilitate corneal nerve regeneration and the restoration of ocular surface health.21 As the final common pathway of chronic ocular surface inflammation may lead to CCH, so too does it increase the risk of neurotrophic keratitis. Such patients can benefit from enhanced tear film and visual stability. Hence, both classically symptomatic and “asymptomatic” (but visually symptomatic) patients deserve the recommendation for restorative ocular surface reconstruction.

There are several well-established techniques utilizing cryopreserved amniotic membrane to provide coverage of the bare scleral defect that functionally reconstruct the fornix tear reservoir following conjunctival excision.22 One such technique provides for the replacement of Tenon’s capsule with a cryopreserved amniotic membrane without excision of the overlying conjunctiva.19 This technique results in a significant increase in basal tear volume correlated with symptomatic resolution, accompanied by significant resolution of corneal staining, conjunctival inflammation, and reduction of topical medications.23 A suture may be used to fixate the amniotic membrane; however, sutureless techniques utilizing fibrin glue may result in greater patient comfort, increased surgical efficiency, and avoidance of suture-related complications.24,20

A traction suture is used at the outset to place the eye in full elevation to not only flatten and avoid trauma to the inferior rectus muscle but also to allow for meticulous excision of diseased Tenon’s and removal and cauterization of prolapsed orbital fat to facilitate better anatomical and functional definition to the fornix tear reservoir upon return to primary gaze. Care should be taken to avoid excessive excision of conjunctiva — in most cases, a crescent-shaped area of the conjunctiva is excised along a limbal peritomy with a maximum anterior-posterior width no more than 3 mm. Once diseased and dissolved Tenon’s are undermined, the overlying conjunctiva lie flat on the globe and recesses itself significantly, leaving a large bare scleral defect. Cryopreserved amniotic membrane is trimmed to shape and size (approximately 25 mm x 10 mm), allowing for adequate excess to tuck under the conjunctival rim. Membrane is peeled from the nitrocellulose backing and slid over the bed of fibrin glue placed on the sclera, effectively coating the stromal underside of the membrane. The tissue is carefully tucked under the conjunctiva to recreate fornix. Excess glue is squeegeed anteriorly toward the cornea to facilitate firm adherence and prevent sequestration of excess glue posteriorly in the newly reconstructed fornix. Immediately postoperatively, the surgeon should note a significantly improved anatomical definition and deepening of the inferior fornix (Figure 2).

FIGURE 2. Before and after sutureless ocular surface reconstruction with cryopreserved amniotic membrane. Preoperatively, significant conjunctival and corresponding lid margin inflammation are noted without obvious conjunctival redundancy (A). Prior to the surgical procedure, significant Tenon’s degeneration, conjunctival laxity, orbital fat prolapse, and obliteration of the inferior fornix are noted (B). A significant reduction in ocular surface and lid margin inflammation are noted postoperatively (C). Intraoperatively, there is immediate restoration of fornix tear reservoir depth and definition (D).
FIGURE 2. Before and after sutureless ocular surface reconstruction with cryopreserved amniotic membrane. Preoperatively, significant conjunctival and corresponding lid margin inflammation are noted without obvious conjunctival redundancy (A). Prior to the surgical procedure, significant Tenon’s degeneration, conjunctival laxity, orbital fat prolapse, and obliteration of the inferior fornix are noted (B). A significant reduction in ocular surface and lid margin inflammation are noted postoperatively (C). Intraoperatively, there is immediate restoration of fornix tear reservoir depth and definition (D).

Final Thoughts

CCH is often overlooked and undertreated, resulting in chronic suffering from ocular surface irritation, redness, foreign body sensation, burning, and pain. It may also be an underlying cause of visual instability in otherwise physically-asymptomatic patients. Surgeons should consider the merits of these various therapeutic approaches. CP

References:

  1. DiPasculae MA, Espana EM, Kawakita T, et al. Clinical characteristics of conjunctivochalsis with or without aqueous tear deficiency. Br. J Ophthalmol. 2004:88:388-392.
  2. Acera A, Vecino E, Duran JA. Tear MMP-9 levels as a marker of ocular surface inflammation in conjunctivochalsis. Invest Ophthalmol Vis Sci. 2013;54(13):8285-8291.
  3. Li DQ, Meller D, Liu Y, Tseng SC. Overexpression of MMP-1 and MMP-3 by cultured conjunctivochalasis fibroblasts. Invest Ophthalmol Vis Sci. 2000;41(2):404-410.
  4. Meller D, Tseng SC. Conjuntivochalasis: literature review and possible pathophysiology. Surv. Ophthalmol. 1998;43(3):225-232.
  5. Balci O. Clinical characteristics of patients with CCH. Clin Ophthalmol. 2014;8:1655-1660.
  6. Nakasato S, Uemoto R, Mizuki N. Thermocautery for Inferior CCH. Cornea. 2012;31(5):514-519.
  7. Zhang XR, Zhang ZY, Hoffman MR. Electrocoagulative surgical procedure for treatment of CCH. Int Surg. 2012;97(1):90-93.
  8. Yang HS, Choi S. New approach for conjunctivochalsis using an argon green laser. Cornea. 2013;32(5):574-578.
  9. Kashima T, Akiyama H, Miura F, Kishi S. Improved subjective symptoms of CCH using bipolar diathermy method for conjunctival shrinkage. Clin Ophthalmol. 2011;5:1391-1396.
  10. Marmalidou A, Palioura S, Dana R, Kheirkhah A. Medical and surgical management of CCH. Ocular Surf. 2019;17(3):393-399.
  11. Braunschweig P. On the development of pleats on the bulbar conjunctiva. Klin Monatsbl. Augenheilkd. 1921;66:123-124.
  12. Lui D. Conjunctivochalasis: A cause for tearing and its management. Ophthalmic Plast Reconstr Surg. 1986;2(1):25-28.
  13. Serrano F, Mora LM. Conjunctivochalasis: a surgical technique. Ophthalmic Surg. 1989;20(12): 883-834.
  14. Yokoi N, Komuro A, Nishii M, et al. Clinical Impact of conjunctivochalsis on the ocular surface. Cornea. 2005;24(8):S24-S31.
  15. Tseng SC, Li DQ, Ma X. Suppression of TGF-β isoforms, TGF-β receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol. 1999;179(3):325-335.
  16. Georgiadis NS, Terzidou CH. Epiphora caused by CCH: treatment with transplantation of preserved amniotic membrane. Cornea. 2001;20(6):619-621.
  17. Meller D, Maskin SL, Pires RT, Tseng SC. Amniotic membrane transplantation for symptomatic CCH refractory to medical treatments. Cornea. 2000;19(6):796-803.
  18. Prabhasawat P, Tseng SC. Impression cytology study of epithelial phenotype of ocular surface reconstructed by preserved amniotic membrane. Arch Ophthalmol. 1997;115(11):1360-1137.
  19. Azuara-Blanco A, Pillai CT, Dua HS. Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol. 1999;83(4):399-402.
  20. Tseng SC. Amniotic membrane transplantation for ocular surface reconstruction. Biosci Rep. 2001;21(4):481-489.
  21. John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. 2017;2017:6404918.
  22. Maskin SL. Effect of ocular surface reconstruction by using amniotic membrane transplant for symptomatic CCH on fluorescein clearance test results. Cornea. 2008;27(6):644-649.
  23. Cheng AM, Yin HY, Chen R, et al. Restoration of fornix tear reservoir in CCH with fornix reconstruction. Cornea. 2016;35(6):736-740.
  24. Fernandez-Hortelano A, Moreno-Montanes J, Heras-Mulero H, Sadaba-Echarri LM. [Amniotic membrane transplantation with fibrin glue as treatment of refractory conjunctivochalasis]. Arch Soc Esp Oftalmol. 2007;82(9):571-574. Spanish.

 

DR. DESAI is director of Cornea, Cataract, and Refractive Services at the Eye Institute of West Florida; medical director, Lions Eye Institute for Transplant and Research; and president and CEO, Clarity Visionary Consulting, all located in Tampa, FL. Disclosures: Tissue Tech/BioTissue.

 

What to Read Next