Descemet's Stripping Without Endothelial Keratoplasty

Daniel Garcerant; Nino Hirnschall; Nicholas Toalster; Meidong Zhu; Li Wen; Gregory Moloney


Curr Opin Ophthalmol. 2019;30(4):275-285. 

In This Article

Noteworthy Clinical Signs

Characteristic clinical signs are associated with this surgery and the resultant healing response. With the addition of topical Rho-kinase inhibitor, different signs emerge.

Contracting Edema/Expanding Clear Zone

Initial dense corneal edema contracts as endothelial migration takes place. The contraction of the area of epithelial edema and formation of a 'clear zone' between descemetorhexis margin and this edema are measurable signs that allow progress to be recorded (Figure 4a).

Figure 4.

(a) Slit lamp photograph demonstrating contracting microcystic edema and formation of a clear zone superiorly and inferiorly (red arrows). (b) Slit lamp photograph demonstrating transformation of microcystic into macrocystic or 'honeycomb' edema on treatment with topical Rho-kinase inhibitor.

Failure to form a clear zone or arrest of the process of contraction are warning signs for failure.

Honeycomb Edema

Of interest, in cases treated with topical Rho-kinase inhibitor the edema adopts a 'honeycomb' appearance with multiple vacuolated fluid cysts within the epithelium (Figure 4b). In our recent series, this finding was not recognized at study commencement but is likely present in all treated cases. The corneal epithelium affected in this way demonstrates a morphologic change in epithelial cells. On confocal microscopy, stratified squamous cells are seen to adopt a more spindle shape at the cyst edge, with loss of cell polarity and organized stratification (Figure 5a). The collapse of the affected cells converts microcystic into macrocystic edema. Histologic analysis failed to demonstrate any evidence of dysplastic or metaplastic change. (Figure 6) These findings are reversible within hours of drop administration and are consistent with the known primary effect of ROCK inhibition – cytoskeletal reorganization and degradation of intercellular junctions. The findings are not found at all in the non edematous corneal epithelium (Figure 5b). Our hypothesis is that cell–cell contact inhibition ameliorates or negates the effect of topical ROCK inhibition. Where this contact is broken down at the site of microcystic edema, ROCK inhibition will produce further cytoskeletal change.

Figure 5.

In-vivo white light confocal microscopy (Confoscan 4; NIDEK Technologies, Padova, Italy). (a) Central corneal epithelium treated with topical ripasudil. Formation of fluid filled macrocysts with spindle cell morphology at cyst edge. (b) Peripheral corneal epithelium from same patient demonstrating preservation of normal cell morphology in non edematous area.

Figure 6.

Light microscopy (H&E stain) of epithelial biopsy in the presence of honeycomb edema. Pale cytoplasm in some cells in presence of edema. Red arrow indicates spindle cell formation at edge of fluid cyst.


In early studies of ROCK inhibitor in human patients 'pseudoguttata' were noted to arise as a transient dark spots or 'cells' visible on specular microscopy, theorized to be due to disruption of actin microfilament bundles and impairment of focal adhesion formation.[14] In vitro analysis of ROCK inhibition in vascular endothelial cells also demonstrated localized gap formation between cells.[56] It is worth noting that these have been described as occurring in many scenarios of ocular inflammation without ROCK inhibition.[57] In subjects treated following DSO with supplementary ROCK inhibitor we have observed similar findings, with guttata like bodies detectable within the stripped area of the cornea in the weeks following surgery (Figure 7c). Confocal microscopy showed these same 'dark bodies' seeming to arise at intercellular junctions rather than within the cytoplasm (Figure 7a and b). We agree that this is likely to represent an interruption of cell adhesion molecules under the influence of ROCK inhibition and should not be mistaken with Fuchs' recurrence. It is most visible in the population of cells migrating to cover the descemetorhexis, presumably where intercellular junctions are most newly formed.

Figure 7.

Endoth pseudoguttata. (a and b) In-vivo white light confocal microscopy (Confoscan 4; NIDEK Technologies, Padova, Italy) images demonstrating round, dark bodies at intercellular junctions (white arrows), correlating to location of pseudoguttata. (c) Slit lamp photograph of pseudoguttata (orange arrows).

Endothelial Pigment Deposition

In several eyes following DSO, we have observed a slow uptake of pigment granules in the stripped area. These are seen as small, darkly pigmented spots that are not affected by application of topical steroid (Figure 8). The ability of the human corneal endothelium to phagocytose circulating aqueous pigment has been documented.[58] Why this is seen in the central stripped area post-DSO is unclear. There may be an increased phagocytic ability in migrating cells with more filopodia, or this may simply be a consequence of polymegathism and a larger cell surface area on which to deposit. Its clinical significance mainly relates to DMEK patients in whom we have observed this sign in the so-called stromal gutter between graft and host, described by Ebru Cömert et al.[59] This phagocytic ability of migrating endothelium should not be mistaken for immunologic rejection in DMEK grafts.

Figure 8.

Slit lamp photograph demonstrating endothelial pigment accumulation within the Descemetorhexis zone.