Potential benefits of modified corneal tissue grafts for keratoconus: Bowman layer 'inlay' and 'onlay' transplantation, and allogenic tissue ring segments.

PURPOSE OF REVIEW: Keratoconus can be surgically challenging, especially in advanced cases. Classic corneal transplantation techniques, may often be associated with complications. New alternative procedures like isolated Bowman layer transplantation (as a corneal stromal inlay or as a corneal onlay) and corneal allogenic intrastromal ring segments (CAIRS) have recently shown promising results. The aim of this review is to describe the main new surgical developments for treating keratoconus. RECENT FINDINGS: Intrastromal Bowman layer transplantation has recently shown to be effective in halting keratoconus progression and maintaining visual acuity with contact lenses, at least up to 5-7 years postoperatively. Because intrastromal dissection can be challenging, we have recently developed a technique that allows using Bowman layer grafts as an onlay, that is positioned onto the patient's anatomical Bowman layer or anterior stroma, achieving comparable results as with Bowman layer inlay transplantation. CAIRS may also be an effective treatment, improving visual acuity, corneal surface parameters and keratoconus progression. SUMMARY: There are currently some new alternative treatments such as isolated Bowman layer inlay or onlay transplantation and CAIRS, both of which seem effective at treating keratoconus and which may offer a less invasive surgical approach.

Bowman layer transplantation: 5-year results.

PURPOSE: The purpose of this study was to evaluate the 5-year clinical results of isolated Bowman layer (BL) transplantation in the treatment of advanced keratoconus. METHODS: In this prospective, single-center, interventional case series at a tertiary referral center, 20 eyes of 17 patients with advanced keratoconus underwent BL transplantation, i.e. an isolated Bowman layer graft was positioned into a manually dissected mid-stromal pocket. Scheimpflug-based corneal tomography measurements, best corrected spectacle and contact lens visual acuities (BSCVA and BCLVA), endothelial cell density, and complications were evaluated up to 5 years after surgery. RESULTS: Measured simulated and maximum keratometry (Kmean and Kmax) values were stable up to 5 years after surgery (P = .310 and P = .195 for 5 years compared to 1 month follow-up, respectively), following an initial decrease from pre- to 1 month postoperatively (P < .001 each). Mean LogMAR BSCVA remained stable (P > .99), after an initial improvement from pre- to 12 months postoperatively (P = .007). Mean BCLVA did not change from preoperative to 5 years postoperatively (P = .219). During all postoperative follow-ups, mean densitometry values were higher than preoperatively (P < .001). A corneal hydrops occurred in one eye at 4.5 years postoperatively; no other postoperative complications were observed. Kaplan-Meier analysis showed an estimated success rate of 84% at 5 years postoperatively. Endothelial cell density remained stable from before to 5 years after surgery (P = .319). CONCLUSIONS: After early postoperative corneal flattening, topographies were stable up to 5 years after BL transplantation, preserving BCLVA and contact lens tolerance, potentially allowing long term postponement of penetrating or deep anterior lamellar keratoplasty.

How Would Nature See Our Corneal Triumphs? The LXXIX Edward Jackson Lecture.

PURPOSE: To describe discrepancies between clinical observation and current teachings in corneal endothelial disease, particularly in Fuchs endothelial dystrophy and its potential association with primary open angle glaucoma. DESIGN: Perspective. METHODS: A perspective is presented on Fuchs dystrophy, a disorder that commonly presents with a compromised endothelium but minimal stromal edema, indicating that the corneal imbibition pressure is relatively "too high." RESULTS: The discrepancy between the relative lack of stromal edema in the absence of an endothelial cell layer cannot be explained by the current theories involving a circulatory pumping mechanism over the endothelial cell layer, but may point to the following: (1) secondary involvement of the corneal endothelium in Fuchs dystrophy; (2) separate hydration systems for maintaining the imbibition pressure (vertical static hydration) and corneal nutrition (horizontal dynamic hydration); (3) the cornea as net contributor of aqueous humor; (4) a close relationship between the corneal imbibition and intraocular pressure, with potentially a shared regulatory system; and (5) a potential steroid-type hormone dependency of this regulatory system. CONCLUSIONS: Clinical observation shows that the stromal imbibition pressure is "too high" in Fuchs endothelial dystrophy, indicating that it may not primarily be an endothelial disease, but a type of "corneal glaucoma."

DMEK Without Postoperative Supine Posturing.

PURPOSE: The purpose of this study was to describe the incidence of graft detachment after Descemet membrane endothelial keratoplasty (DMEK) without postoperative supine posturing. METHODS: A total of 106 eyes of 84 patients with Fuchs endothelial corneal dystrophy or bullous keratopathy (BK) were operated by a single experienced surgeon with DMEK with a 99% anterior chamber air bubble fill, recovered in an upright (seated) position, and then discharged without instructions to remain supine. Postoperatively, all eyes were evaluated for graft detachment through anterior segment optical coherence tomography at predetermined intervals (1 d, 1 wk, and 1 mo). Detachments were regarded as clinically significant if they subtended 30% of the total graft surface area or involved the visual axis. RESULTS: Clinically significant graft detachments were observed in 23 of 106 eyes (22%) in the no-supine posturing cohort, including 22 of 85 eyes (26%) operated for Fuchs endothelial corneal dystrophy and 1 of 21 eyes (5%) operated for BK. Compared with a historical comparison group of eyes undergoing DMEK with 48 hours of postoperative supine posturing, the risk of graft detachment was not increased. In both cohorts, 6% of operated eyes required regrafting for either persistent detachment or primary graft failure. No additional intraoperative or postoperative complications were experienced. CONCLUSIONS: Particularly in eyes operated for BK, the supine posturing requirement after DMEK may be eliminated without increasing the absolute risk for clinically significant graft detachment.

Intracorneal ring segment implantation in advanced Keratoconus.

PURPOSE: To compare the clinical outcomes of intracorneal ring segment (ICRS) implantation in eyes with advanced vs. mild/moderate keratoconus (KCN). METHODS: A retrospective analysis of 141 eyes of 111 patients with KCN who underwent ICRS implantation. Preoperative maximum keratometry (Kmax) was <57 diopters (D) in 70 eyes and >57 D in 71 eyes. Postoperatively, corrected distance visual acuity (CDVA), Kmax, and intraoperative and postoperative complications were assessed at 1 day, 1 month, and 1 year. RESULTS: Corneas with a preoperative Kmax >57 D experienced greater reduction in axial curvature after ICRS implantation than corneas with a preoperative Kmax <57 D (7.0 D vs. 5.5 D, p=0.005) and gained more Snellen lines of CDVA (3 vs. 1, p<0.001) by 1 year postoperatively. The incidences of the most prevalent complications (explantation, extrusion, and infectious keratitis) did not differ significantly between the two groups (p=0.29, p=0.99, p=0.98). CONCLUSIONS: The visual and topographic effects of ICRS implantation are greater in eyes with more advanced KCN, with no increase in the incidence of the most common complications.

Clinical outcomes of Descemet membrane endothelial keratoplasty performed in eyes with keratoconus and corneal endothelial dysfunction.

PURPOSE: To evaluate the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) performed in eyes with comorbid keratoconus (KCN) and corneal endothelial dysfunction. METHODS: Twenty-five consecutive eyes of 14 patients with comorbid stable KCN underwent DMEK for corneal endothelial dysfunction; best spectacle corrected visual acuity (BSCVA), maximum corneal curvature (Kmax), maximum corneal power (Pmax), central corneal thickness (CCT), and intra- and postoperative complications were assessed. RESULTS: Excluding eyes requiring re-transplantation for primary graft failure (n = 3), all eyes showed improvement in BSCVA, reaching ≥ 20/40 (0.5) in 86%, ≥ 20/25 (0.8) in 55%, and ≥ 20/20 (1.0) in 27% by one month postoperatively; 90%, 76%, and 48% by 6 months postoperatively; and 88%, 76%, and 47% by 12 months postoperatively. CCT decreased from 571µm preoperatively to 485µm at 1 month (p < 0.001) and 481µm at 12 months (p < 0.001). Kmax decreased by a median of 1.4 diopters (D) at 1 month (p = 0.003) and 3.1 D at 12 months (p = 0.021), and every eye with a preoperative Kmax ≥ 46 D demonstrated flattening. Pmax decreased by 2.1 D at 1 month (p = 0.001) and 4.0 D at 12 months (p = 0.016). CONCLUSION: DMEK is technically feasible in eyes with comorbid KCN and may give excellent outcomes visual and refractive outcomes, including significant corneal flattening, which may potentially create a visually significant hyperopic shift in patients with severely ectatic corneas.

DMEK with endophotocoagulation and cyst wall removal for corneal endothelial decompensation due to iris cyst.

PURPOSE: Iris cysts may arise secondary to surgical or nonsurgical trauma, potentially leading to corneal decompensation via mechanical injury to the adjacent endothelium. However, no well-established protocol exists for the treatment for corneal edema arising therefrom. OBSERVATIONS: A 58-year-old white male presented with an iris mass of his left eye; it occupied 1/3rd the anterior chamber volume and directly contacted the corneal endothelium. The cornea was diffusely edematous, and best corrected visual acuity (BCVA) measured 20/70 (0.3). Corneal endothelial decompensation secondary to iris cyst was diagnosed. Treatment consisted of endophotocoagulation and vitrectomy probe removal of the cyst wall, with Descemet membrane endothelial keratoplasty (DMEK) also performed as a single, combined procedure. The patient subsequently experienced a resolution of his corneal edema and disappearance of his iris cyst, without recurrence of either condition. BCVA improved to 20/25 (0.8). CONCLUSIONS AND IMPORTANCE: Iris cyst may be a rare cause of corneal decompensation. Viable treatment may entail a single-stage procedure involving endophotocoagulation and vitrectomy probe application to the cyst wall combined with DMEK.

Bowman Layer Onlay Graft for Recurrent Corneal Erosions in Map-Dot-Fingerprint Dystrophy.

PURPOSE: The purpose of this study was to describe a case with recurrent corneal erosions who was treated with a Bowman layer (BL) onlay graft. METHOD: BL onlay transplantation was performed. RESULTS: In a 79-year-old female patient who presented with bilateral map-dot-fingerprint dystrophy and a history of recurrent painful corneal erosions, BL onlay grafting was performed to restore the corneal surface. At 1 month postoperatively, the epithelium was smooth over the graft, and until 1.5 years postoperatively, the patients had no complaints and no recurrence of the epithelial corneal erosion. CONCLUSIONS: In the described case, the transplantation of an isolated BL graft as an onlay proved to be an effective treatment for painful chronic recurrent erosions in the context of map-dot-fingerprint dystrophy in a patient who had undergone numerous unsuccessful previous treatments.

Preimplantation dehydration for corneal allogenic intrastromal ring segment implantation.

Corneal allogenic intrastromal ring segments (CAIRS) are semicircular pieces of donor corneal stroma, which may be surgically implanted to flatten keratoconic corneas. These segments can be trimmed to different thicknesses; whereas thicker segments confer greater flattening, their bulk renders them more technically challenging to insert. Consequently, thinner segments are often preferred, especially for starting surgeons. Here, we describe a technique for transiently thinning CAIRS to facilitate easy insertion, thereby permitting the use of thicker segments to achieve the maximal flattening effect.

Flattening the curve: manual method for corneal allogenic intrastromal ring segment implantation.

Corneal allogenic ring segments are semicircular pieces of donor corneal stroma that may be surgically implanted to flatten keratoconic corneas. Conventionally, these donor segments are inserted into channels created using femtosecond laser dissection. However, access to femtosecond technology is not universal. In this study, an alternate, manual technique for channel creation, which is femtosecond laser independent, is described.

Bowman Layer Onlay Grafting: Proof-of-Concept of a New Technique to Flatten Corneal Curvature and Reduce Progression in Keratoconus.

PURPOSE: The aim of this study was to describe a new surgical technique for flattening the corneal curvature and to reduce progression in eyes with advanced progressive keratoconus (KC) by using Bowman layer (BL) onlay grafting and to report on the preliminary outcomes of this procedure. METHODS: In this prospective interventional case series, 5 patients with advanced progressive KC underwent BL onlay grafting. After removal of the epithelium, a BL graft was placed and "stretched" onto the stroma, and a bandage lens was placed to cover the BL graft. In 1 case, BL onlay grafting could be performed immediately after ultraviolet corneal crosslinking; all other eyes were ineligible for ultraviolet corneal crosslinking. Best spectacle- and/or best contact lens-corrected visual acuity, refraction, biomicroscopy, corneal tomography, anterior segment optical coherence tomography, and complications were recorded at 1 week and at 1, 3, 6, 9, and 12 to 15 months postoperatively. RESULTS: All 5 surgeries could be performed successfully. Average maximum keratometry went from 75 diopters (D) preoperatively to 70 D at 1 year postoperatively. All eyes showed a completely reepithelialized and a well-integrated graft. Best spectacle-corrected visual acuity improved at least 2 Snellen lines (or more) in 3 of 5 cases and best contact lens-corrected visual acuity remained stable, improving by 3 Snellen lines in case 1 at 15 months postoperatively. Satisfaction was high, and all eyes again had full contact lens tolerance. CONCLUSIONS: BL onlay grafting may be a feasible surgical technique, providing up to -5 D of corneal flattening in eyes with advanced KC.

Bowman Layer Transplantation-A Review.

Bowman layer (BL) transplantation has been described for various indications, including the treatment of postrefractive corneal haze, postherpetic scarring, and keratoconus. The unique properties of the BL explain its versatility. Robust, thin, and acellular, transplanted BL inhibits stromal scarring, flattens ectatic corneas, and poses minimal risk of immune reaction. This article reviews the history of BL transplantation and recent developments, and anticipated next steps for the procedure.

"Double-Bubble" Descemet Membrane Endothelial Keratoplasty Unfolding in Eyes With Deep Anterior Chambers and Anterior Chamber Intraocular Lenses.

PURPOSE: To describe a standardized technique for Descemet membrane endothelial keratoplasty unfolding in eyes with deep anterior chambers and anterior chamber intraocular lenses (ACIOLs). METHODS: Two air bubbles are used simultaneously: the first placed on top of the graft and the second one underneath. RESULTS: The 2 bubbles work in concert-the bubble on top props the tissue partially open, while the bubble underneath levitates the graft away from the ACIOL and provides support for subsequent unfolding maneuvers. CONCLUSIONS: By sandwiching the graft between 2 bubbles, unfolding may proceed away from physical contact with the ACIOL, even in eyes with hyper-deep chambers.

Suprachoroidal Hemorrhage During Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe two cases of suprachoroidal hemorrhage during Descemet membrane endothelial keratoplasty (DMEK). METHODS: Two patients with pseudophakic bullous keratopathy (PBK) underwent DMEK and proceeded to develop intraoperative suprachoroidal hemorrhage. Reports of both cases are documented, including potential risk factors, intraoperative events, and postoperative outcomes and interventions. RESULTS: Both cases required premature abortion of the operation following the abrupt onset of significant posterior pressure indicating potential suprachoroidal hemorrhage. Postoperative visual acuity measured light perception or worse, and both patients declined further intervention. CONCLUSIONS: Suprachoroidal hemorrhage is a rare but potentially devastating intraoperative complication which may occur during DMEK, particularly in eyes with relevant risk factors. An inability to deepen the anterior chamber following graft implantation may signify the condition.

Bowman Layer Onlay Graft for Reducing Fluctuation in Visual Acuity After Previous Radial Keratotomy.

PURPOSE: To describe the clinical outcome of a first patient undergoing Bowman layer (BL) transplantation with an onlay graft to reduce fluctuation in visual acuity and refractive error after previous radial keratotomy (RK) surgery. METHODS: In 2018, a 66-year-old woman presented with complaints of long-standing diurnal fluctuation in best-spectacle corrected visual acuity (BSCVA) after RK in 1983. After the removal of host epithelium, a BL graft was positioned onto the host cornea. BSCVA, Scheimpflug-based corneal tomography, and anterior segment optical coherence tomography were evaluated up to 12 months postoperatively. RESULTS: The surgery and postoperative course were uneventful. After surgery, the subjective complaints of visual fluctuation were reduced from 10 to 3 on a scale from 1 to 10. BSCVA (20/40; 0.5) did not change from preoperative to postoperative. Corneal tomography showed an overall central corneal steepening of 5.9 diopters. Biomicroscopy, Scheimpflug imaging, and anterior segment optical coherence tomography showed a completely epithelialized and well-integrated graft, with some minor epithelial remnants located in the preexisting keratotomy incisions. CONCLUSIONS: BL onlay grafting may have the potential to manage patients with subjective complaints of diurnal fluctuation in visual acuity after previous RK.

DMEK in Super-Seniors: Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty Performed in Patients ≥ 90 Years Old.

PURPOSE/AIMS OF THE STUDY: To evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed in the "oldest old" patients, i.e. ≥ 90 years. MATERIALS AND METHODS: Between the years of 2009 and 2019, 20 consecutive eyes of 17 patients aged ≥ 90 underwent DMEK for endothelial dysfunction. Best corrected visual acuity (BCVA), central corneal thickness (CCT), endothelial cell density (ECD), graft survival, and intra- and postoperative complications were assessed. RESULTS: Except in one case in which the DMEK surgery could not be completed, all operated eyes experienced an improvement in BCVA, although only 50% achieved ≥ 20/40 (0.5) by 1 year postoperatively. One year after surgery, median CCT had declined from 641(±161) µm to 480 (±34) µm, and median endothelial cell density was reduced by 53%, from 2574 (±286) to 1226 (±404) cells/mm2. Six of 19 eyes receiving DMEK grafts (32%) developed partial graft detachments requiring re-bubbling. One eye experienced a secondary graft failure at 6 months and underwent repeat endothelial keratoplasty. CONCLUSION: DMEK is technically feasible in the oldest old patients and may yield significant visual improvements, although an elevated risk of some postoperative complications including graft detachment with corresponding need for re-bubbling may be anticipated.

Bowman Layer Onlay Transplantation to Manage Herpes Corneal Scar.

PURPOSE: To introduce the concept of using a Bowman layer (BL) onlay graft to manage superficial herpetic corneal scarring and to describe the clinical outcomes of the first 2 cases undergoing this procedure. METHODS: Two patients with a quiescent superficial corneal scar after herpes (varicella zoster virus [n = 1] and herpes simplex virus [n = 1]) keratitis underwent BL onlay transplantation. After the removal of the host epithelium and limited superficial keratectomy, an isolated BL graft was placed onto the host corneal surface. The cornea was then covered with an amniotic membrane and a bandage contact lens. Best spectacle-corrected visual acuity (VA) and/or best contact lens-corrected VA (BCLVA), biomicroscopy, corneal tomography, and anterior segment optical coherence tomography were recorded at 1 week, 1 month, and 3, 6, 9, 12, and 18 months postoperatively. RESULTS: In both cases, the surgical and postoperative courses were uneventful. An improvement of the corneal clarity was observed at biomicroscopy, and no varicella zoster virus/herpes simplex virus reactivation occurred throughout the follow-up period. Biomicroscopy, Scheimpflug imaging, and anterior segment optical coherence tomography showed a completely epithelialized and well-integrated graft postoperatively. In case 1, BCLVA with a scleral lens improved from 20/100 (0.1) preoperatively to 20/32 (0.6) postoperatively. For case 2, no preoperative BCLVA was available, but a BCLVA of 20/36 (0.55) was achieved after the procedure. CONCLUSIONS: A BL onlay graft may be a feasible surgical procedure, which may have the potential to reduce superficial corneal scarring and/or anterior corneal irregularities without resorting to deeper keratoplasty in these complex cases.

Perceived difficulties and barriers to uptake of Descemet's membrane endothelial keratoplasty among surgeons.

Purpose: To determine barriers related to implementation of Descemet's membrane endothelial keratoplasty (DMEK) among corneal surgeons. Methods: This was a multicenter survey study of all corneal surgeons who participated in a DMEK wet lab organized by the Netherlands Institute for Innovative Ocular Surgery. Data related to barriers limiting uptake of DMEK surgery, self-perceived levels of competence, and difficulty with different steps of DMEK surgery were analyzed. Results: The survey response rate was 31% (22 of 72). The most common barrier to uptake of DMEK surgery identified was anxiety related to incorrect insertion of the tissue and the need to regraft (64%, 14 of 22), followed by anxiety related to tissue preparation (50%, eleven of 22). Surgeons also felt anxious regarding the possibility of rebubbling with initial DMEK (41%, nine of 22). Steps related to DMEK graft (76%) preparation, tissue insertion (41%), and graft unfolding (72%) were identified as the most difficult steps to learn by the respondents. Conclusion: The DMEK learning curve, especially for the novice surgeon, may be shortened by seeking educational resources, including wet labs and surgical videos. Eye banks may facilitate adoption of DMEK by making validated DMEK tissue more accessible to surgeons globally.

Corneal ulceration associated with Nivolumab use.

PURPOSE: To describe a case of corneal ulceration associated with Nivolumab use. OBSERVATIONS: An 80-year-old woman treated with Nivolumab for metastatic melanoma developed an intractable corneal ulcer in her left eye, refractory to all therapies - including surgery to cover the ulcer with a conjunctival flap - until topical prednisolone acetate was tried, which was curative. CONCLUSIONS AND IMPORTANCE: Nivolumab use may be associated with a form of steroid-responsive corneal ulceration.