THE ENDOTHELIUM is a monolayer of cells on the posterior corneal surface whose primary function is to transport water from the stroma into the anterior chamber to maintain corneal thickness and clarity (Tuft and Coster, 1990). Without proper endothelial function, the cornea would naturally imbibe aqueous from the anterior chamber, which would ultimately result in corneal edema and reduction of corneal transparency (Chaurasia and Vanathi, 2021; Gupta et al, 2021).

 

The human corneal endothelium does not regenerate. Therefore, any damage to endothelial cells is repaired only by migration and expansion of surviving cells. Endothelial health is interpreted with parameters such as percentage of hexagonal endothelial cells, coefficient of variation of cell size, and endothelial cell density (Figure 1).

Abnormality of endothelial cell size variability is termed “polymegethism.” Abnormality in the percentage of hexagonally shaped cells is termed “pleomorphism.” One of the most common abnormalities referred to in regard to corneal endothelial cell health is a reduction of cell density, often referred to as reduced “cell count” (Chaurasia and Vanathi, 2021) (Figure 2).

Under normal circumstances, the corneal endothelial cell density declines throughout life at an average rate of 0.6%/year (Bourne et al, 1997). At birth, human endothelial cell density is approximately 5,000 to 6,000 cells/mm², but it gradually decreases to about 3,500 cells/mm² by 5 years of age, 3,000 cells/mm² by age 14 to 20 years, and 2,500 cells/mm² in late adulthood (Chaurasia and Vanathi, 2021; Gupta et al, 2021). Numerous elements can have a negative impact on corneal endothelial cell health, including corneal degenerations/dystrophies, trauma, and ocular surgery, among others.

Corneal endothelial cell layer imaging and analysis is typically performed with either specular microscopy or confocal microscopy. Although specular microscopy is more common clinical practice, there are reports that confocal imaging may be more successful in cases of more advanced corneal disease states (Hara et al, 2003).

ENDOTHELIAL ABNORMALITIES

Corneal Dystrophies and Degenerations Primary endothelial disorders are exemplified by Fuchs’ endothelial corneal dystrophy (FECD). Abnormalities in FECD typically begin in the central cornea and progress peripherally and include findings such as guttata and cell dropout (Zhang et al, 2020).

Other conditions in this category include posterior polymorphous dystrophy and iridocorneal endothelial (ICE) syndrome. The endothelial status in keratoconus has been reported to be normal in early stages of the disease; however, in more advanced stages, cell density is reduced and degrees of polymegethism and pleomorphism are increased (Elmassry et al, 2021).

Ocular Procedures and Surgery A number of ocular surgical procedures can result in abnormalities of the endothelium. Cataract surgery can result in progressive corneal endothelial abnormalities, including reduction of cell count and progressive morphological changes to endothelial cells. If damage is highly significant, this can result in postsurgical corneal edema that can develop into pseudophakic bullous keratopathy (PBK) (Gurnani and Kaur, 2022). Fortunately, contemporary surgical techniques have significantly reduced the amount of endothelial damage and frequency of PBK.

Keratoplasty procedures also impact endothelial health status. Penetrating keratoplasty (PK) results in rapid reduction of endothelial cell density over the initial five years following surgery and tends to progress at a much lower rate out to 10 years (Lass et al, 2013).

Studies have also looked at the long-term effects of laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) on the corneal endothelium and concluded that this is not the case (Patel and Bourne, 2009; Klingler et al, 2012). As an example, one study found that endothelial cell density at nine years after LASIK and PRK decreased by 5.3% from preoperative (p < 0.001, n = 29), whereas coefficient of variation of cell area and percentage of hexagonal cells did not change (p = 0.24 and p = 0.19, respectively, n = 29) (Patel and Bourne, 2009). The annual rate of cell loss after refractive surgery (0.6% ± 0.8%) was not different from that in normal corneas (0.6% ± 0.5%, p = 0.88; minimum detectable difference = 0.5%, α = 0.05, β = 0.20) (Patel and Bourne, 2009).

The influence of corneal cross-linking (CXL) on corneal endothelial cell health has been a topic of concern since the procedure’s development. It is suggested that the pretreatment corneal thickness should be at least 400μm to prevent corneal endothelial cell damage caused by UV-A irradiation (Spoerl et al, 2007). The cytotoxic dose of UV radiation to the corneal endothelium is 0.65 J/cm² (Wollensak et al, 2003). Typical levels of UV radiation reaching the endothelium in CXL with corneas of at least 400μm thick is a factor of two smaller than the damage threshold (Spoerl et al, 2007).

INFLUENCE OF CONTACT LENS WEAR

Generally, corneal endothelial effects from contact lens (CL) wear can be divided into two categories: transient and long term (Schoessler, 1991). Transient endothelial response to CL wear has been reported to express as bleb formation.

Endothelial blebs were first described by Zantos and Holden (1977). These dark areas in the endothelial mosaic pattern are maximally observed 25 to 30 minutes after placing a rigid or soft lens of low oxygen transmissibility on an eye that was previously unadapted to CL wear. The blebs gradually fade away as CL wear continues past two hours (Schoessler, 1991).

Long-term endothelial response to CL wear is evaluated based on the effect on cell density, size variation, and shape anomalies. Thought to be due to hypoxic influences, abnormalities from CL wear include both polymegethism and pleomorphism (Schoessler, 1991). Less common is abnormal reduction in cell density with CL wear (Liesegang, 2002). The term “contact lens endotheliopathy” has been used to describe these abnormalities (Epshtein, 2019; Thomas, 2009).

Duration of CL wear seems to be correlated with increasing CL endotheliopathy (Lee et al, 2001; Chang et al, 2001). A study of 90 soft CL wearers were divided into three groups: short-term users, for less than five years (n = 60 eyes); intermediate-term users, from six to 10 years (n = 60); long-term users, for more than 10 years (n = 60) (Lee et al, 2001). Thirty non-CL wearers (60 eyes) were included as controls. Results indicated that there was a significant correlation between duration of soft CL use and morphologic changes of the corneal endothelium.

Concern regarding hypoxia in scleral CL wear due to lens thickness, fluid reservoir thickness, and lack of significant movement and tear exchange has been ongoing. However, a study of corneal response to scleral CL wear in keratoconus found that daily wear of sclerals lenses in patients who had keratoconus was not associated with adverse effects on the cornea or endothelium over a period of 90 days (Cagliari et al, 2022).

CONCLUDING REMARKS

The corneal endothelium performs a critical function to maintain thickness and clarity in response to the natural tendency of the stroma to imbibe aqueous. Clinical endothelial evaluation is highly valuable. CLS

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