Cornea最新文献

Purpose: Total limbal stem cell deficiency (LSCD), severe dry eye disease (DED), and ocular surface keratinization are severe ocular complications of Stevens-Johnson syndrome (SJS) that can be difficult to manage, resulting in poor visual outcomes. Several ocular surface reconstruction and visual rehabilitation techniques have been attempted with no satisfactory outcomes to date. Our purpose is to assess the functional and anatomical outcomes of Boston keratoprosthesis type I (Kpro-I) after minor salivary glands transplantation (mSG) and labial mucous membrane (MMG) grafting in patients with SJS suffering from total LSCD, DED, and ocular surface keratinization.

Methods: This is a retrospective multicenter case series from 2 tertiary referral centers (New England Eye Center, Tufts Medical Center, Boston, Massachusetts and Federal University of Sao Paulo) assessing long-term outcomes of patients with SJS with severe ocular complications who received mSG/MMG grafting before Kpro-I implantation, including best-corrected visual acuity, Kpro-I device retention, and postoperative complications.

Results: Three patients with SJS with severe ocular complications (total LSCD, symblepharon, DED, and ocular surface keratinization) were treated with mSG/MMG grafting, followed by Kpro-I. Ocular surface keratinization was ameliorated in all patients after mSG. At the end of the long-term follow-up period, all patients retained the Kpro-I (33-63 months) and achieved improved visual acuity (20/40, 20/80, 20/100). Complications included glaucoma (n = 1), requiring a glaucoma drainage device; peripheral corneal thinning (n = 2), which was treated with a corneal patch graft; postoperative infectious keratitis (n = 1); cystoid macular edema (n = 1); and retroprosthetic membrane (n = 1), which was successfully treated.

Conclusions: mSG/MMG grafting can optimize the ocular surface to allow for successful Kpro-I in patients with severe SJS, providing an alternative approach to Boston type II Kpro.

Purpose: To compare biomarker expression and proliferation rates of limbal epithelial stem cells (LESCs) cultured on Descemet membrane (DM) versus amniotic membrane (AM). To investigate the suitability of DM as a potential long-term scaffold for transplantation of cultivated limbal stem cells on the ocular surface.

Methods: Donor limbal epithelial cells were pooled, reseeded, and expanded on decellularized DM and AM. LESC biomarker expression was assessed by In-Cell Western and immunocytochemical staining. Cell proliferation was evaluated by BrdU incorporation. Airlift organ cultures were performed on DM-limbal tissue constructs and analyzed with 3D immunofluorescence microscopy to determine if DM could support stratified epithelial growth. Suitability of DM as a potential long-term scaffold for cultured LESCs on the cornea was assessed by evaluating transparency and resistance to collagenase digestion versus AM.

Results: Cultured cells exhibited higher expression of putative LESC markers (ABCG2, ABCB5), lower expression of transient amplifying cell marker (p63α), and lower cell proliferation rates on DM versus AM, indicating DM maintained LESC stemness better than AM. Under airlifting conditions, cells on DM stratified with differentiation and expression of corneal epithelial cell biomarkers in superficial layers, while maintaining LESC biomarker expression in basal layers. DM was more transparent and resistant to collagenase digestion than AM.

Conclusions: DM promotes LESC stemness better than AM in ex vivo culture and can support stratified corneal epithelium. DM is also a more transparent and potentially durable epithelial scaffold than AM. DM is a promising new alternative to AM for limbal stem cell therapy.

Purpose: To compare the diagnostic performance of traditional microbiologic tests and next-generation sequencing methods for infectious keratitis pathogen detection.

Methods: Participants included 86 subjects diagnosed with acute infectious keratitis at Aravind Eye Hospital in Madurai, India. Corneal scrapings from all subjects were evaluated using Gram stain, potassium hydroxide (KOH) smear, culture, and metagenomic deep sequencing (MDS). The sensitivity and specificity of each test were estimated using latent class analysis.

Results: Among 86 participants, clinical diagnostic tests demonstrated varying sensitivity and specificity for bacterial and fungal keratitis. Gram stain exhibited high sensitivity (89%) and specificity (94%) for bacterial detection, whereas KOH smears showed only moderate sensitivity (75%) and specificity (69%) for fungal detection. Culture testing had lower sensitivity for bacterial (68%) and fungal (56%) identification, but high specificity (92% and 88%, respectively). MDS demonstrated the best balance of sensitivity and specificity across pathogen classes, with 100% sensitivity and 90% specificity for bacterial keratitis and 82% sensitivity with 94% specificity for fungal keratitis. MDS detected critical pathogens missed by culture in 29% of cases, including those whose identification is essential for guiding clinical management and preventing vision-threatening complications.

Conclusions: MDS demonstrated a favorable balance between sensitivity and specificity for both bacterial and fungal keratitis, whereas smears performed well for bacterial but not fungal keratitis and cultures demonstrated high specificity but low sensitivity. Repeated evaluation of diagnostic performance across diverse populations and geographic settings is necessary to validate the reliability and optimize the clinical utility of microbiologic testing for infectious keratitis.

Purpose: To assess the effect of surgical decision making on the type of corneal crosslinking (CXL) protocol in eyes with keratoconus (KC) based on stromal thickness maps and thinnest corneal pachymetry (TCP).

Methods: A prospective, nonrandomized cohort study was performed between January 2022 and January 2023. Patients were allocated to Epi-off or transepithelial CXL (TE-CXL) procedures depending on the TCP value using Scheimpflug. TCP ≥450 μm was used to designate patient's eye to the Epi-off CXL procedure and TCP <450 μm to TE-CXL. On the same day, a combined Placido and Anterior Segment OCT evaluation was performed to assess epithelial thickness (ET) and minimum stromal thickness (MinST). The type of surgery was then finally selected: Epi-off CXL was indicated when MinST ≥400 μm, whereas TE-CXL procedure was indicated when MinST <400 μm. We assessed the percentage of cases in which MinST data changed the surgical decision (Utility).

Results: The study included 245 eyes, MinST was 407.26 ± 50.92 (range 223-497). Stromal thickness maps assessed before surgery altered the surgeon's decision making in 5.30% (13 out of 245) of cases. The procedure was changed from Epi-off to TE-CXL and from TE-CXL to Epi-Off in 3.67% and 1.63% of the cases, respectively.

Conclusions: Anterior segment optical coherence tomography stromal thickness maps have minimal impact on the surgical decision making for conventional Epi-off and TE-CXL protocols. Considering that MinST data provide objective information on stromal thickness, unlike TCP, and avoid the need for deepithelialization, their implications in sub-400 protocols may be greater.

Purpose: To investigate whether stress distribution patterns can predict biomechanical progression in keratoconus eyes using longitudinal data.

Methods: The corneal contribution to stress, (CCS) = r/2t, was calculated based on the Hoop stress formula without intraocular pressure. Here, r is radius of curvature and t is corneal thickness. CCS was calculated from Pentacam tangential curvature and thickness maps (Oculus, Wetzlar, Germany) and investigated the difference in magnitude of stress between the 2-mm zones of minimum and maximum CCS (CCSmin, CCSmax), and the difference between them (CCSdiff). We included patients with diagnosed keratoconus and healthy controls. Exclusion criteria were use of contact lenses, previous corneal surgery, corneal scar, other corneal diseases, and bad quality of Pentacam images. A linear mixed model was used to determine predictive ability of CCSdiff. A P-value <0.05 was considered significant.

Results: A total of 114 eyes of 70 patients with keratoconus and 31 eyes of 31 healthy controls were included with a mean age of 24 ± 6 and 24 ± 4 years, respectively. Patients with keratoconus had a mean follow-up time of 2 years (range 0.2-13.6 years). At baseline, in keratoconus, CCSmax was 8.3 ± 1.1 and CCSmin was 6.6 ± 0.6. For healthy eyes, mean values were 7.4 ± 0.5 and 6.5 ± 0.5, respectively. CCSdiff correlated significantly with maximum zonal tangential curvature (Cspot) (r = 0.83, P < 0.001). CCSdiff at baseline predicted progression over time of Cspot (P < 0.001).

Conclusions: The difference between minimum and maximum stress contribution, CCSdiff, changes in time, and its baseline values predict progression in patients with keratoconus.

Purpose: To compare graft survival and alloimmune responses in murine endothelial keratoplasty (EK) versus penetrating keratoplasty (PK) and to elucidate the immunological mechanisms that underlie the differential graft outcomes.

Methods: Allogeneic EK and PK were performed in BALB/c recipient mice using fully disparate C57BL/6 donors; syngeneic EK recipients served as controls. Graft clarity was monitored over 16 weeks by slitlamp biomicroscopy and scored using standardized opacity grading. Anterior segment optical coherence tomography (AS-OCT) was used to measure central corneal thickness. Graft survival was assessed using Kaplan-Meier analysis. Immunohistochemistry and confocal microscopy were performed to evaluate corneal endothelial cell (CEnC) integrity through ZO-1 staining. T-cell-mediated alloimmunity was assessed using intracellular IFN-γ staining (flow cytometry) and ELISPOT assays targeting both direct and indirect antigen presentation pathways.

Results: PK allografts exhibited significantly higher corneal opacity and lower survival (50%) than allogeneic EK grafts (71.4%, P < 0.0001). AS-OCT showed that corneal edema was highest in rejected PK grafts at 4 weeks and in rejected EK grafts at 16 weeks, with EK displaying a more gradual increase in thickness. Flow cytometry revealed significantly greater frequencies of IFN-γ+CD4+ T cells in PK recipients compared with EK recipients (P < 0.001). ELISPOT assays demonstrated a more robust Th1 response in PK through both the direct and indirect sensitization pathways. Corneal endothelial cell (CEnC) density was significantly reduced in rejected EK and PK grafts compared with their respective accepted counterparts (P < 0.01), whereas CEnC density was comparable between accepted EK and PK grafts.

Conclusions: EK grafts exhibit higher graft survival rates and significantly reduced activation of host T-cell responses compared with PK grafts, which may be attributed to lower frequencies of graft-borne antigen presenting cells, thus resulting in a milder Th1-mediated immune response.

Purpose: In patients with severe ocular surface disease (OSD) and cornea and cataract-related vision impairment, where the risk of allograft rejection after allogeneic corneal transplantation is unacceptably high and cataract surgery impossible because of corneal opacity, cataract extraction may still offer meaningful improvement in vision-related quality of life. We describe ipsilateral, nonrotational autokeratoplasty (INRA) as option to perform open-sky cataract surgery after removal of the central cornea and prevent immune responses by placing back the original host cornea.

Methods: This report presents 2 patients with only 1 functional eye, cataract and severe OSD (Lyell syndrome, chemical burn) undergoing INRA to enable cataract surgery as an alternative approach to visual rehabilitation, aiming to avoid high-risk corneal transplantation. Both patients had a small central zone of relative corneal clarity.

Results: This is the first report of INRA for concomitant cataract surgery. Postoperatively, both visual acuity and patient-reported visual satisfaction improved. In 1 case, delayed wound healing was noted and successfully managed with standard treatments. No other severe complications, adverse events, or rejection episodes were observed.

Conclusions: Although INRA does not address corneal vision impairment, it allows effective cataract management in patients with relative central corneal clarity and otherwise very high risk for corneal allograft failure.

Purpose: To evaluate recent literature to determine the incidence and microbiology of endophthalmitis in eyes with the type 1 Boston Keratoprosthesis (BKPro).

Methods: A literature review was performed using PubMed, Embase, and Cochrane databases. Studies were included if published ≥2010, included ≥20 BKPro eyes, and reported the mean follow-up time. Studies with duplicate data sets or limited to 1 type of underlying condition or age group were excluded. A meta-analysis was performed to calculate endophthalmitis incidence (cases per 100 eye-years).

Results: Of 501 studies reviewed, 34 met inclusion criteria; these included 2732 BKPro eyes. The mean follow-up (range 1.4-8.9 years) was <5 years in 85% of studies. A total of 161 eyes developed endophthalmitis. Most studies reported the proportion of their cohort that developed endophthalmitis (0%-22%) but not the incidence. The pooled mean incidence of endophthalmitis was 2.09 cases per 100 eye-years (95% CI, 1.63-2.67). In 44 endophthalmitis cases with complete microbiology, 54.5% were bacterial (two thirds because of gram-positive bacteria), 29.5% fungal (primarily Candida), and 16% no growth. Some cases occurred despite topical antibiotics effective against the endophthalmitis pathogen. Risk factors included antecedent keratitis, noncompliance with prophylactic antibiotics, corneal melt around the BKPro, and an exposed glaucoma drainage device.

Conclusions: The incidence of endophthalmitis in BKPro eyes is 2 cases per 100-eye years, based on 34 recent studies with relatively short follow-up times. Future studies should report endophthalmitis incidence rather than proportion. More studies with long follow-up times will be helpful in determining the 5- and 10-year risk of endophthalmitis.

Purpose: This study assessed corneal tomographic, biomechanical, and pachymetry using 3 multimodal imaging (MMI) diagnostic capabilitiesto detect keratoconus in first-degree relatives (FDR) of patients with keratoconus and normal populations.

Methods: This was a prospective cross-sectional study. A total of 118 eyes from 78 patients with keratoconus, 96 eyes from 54 FDR subjects, and 126 eyes from 63 healthy individuals were analyzed using the Oculus Pentacam HR, Oculus Corvis ST, and Cirrus OCTA 5000. Corneal tomography, biomechanics, and pachymetry were performed and compared between the 3 groups.

Results: Notable disparities in corneal tomography, biomechanics, and pachymetry were observed between FDR and healthy subjects. FDR exhibited a thinner cornea and reduced corneal biomechanical strength compared with normal eyes. In distinguishing keratoconus in FDR, the diagnostic capabilities of B.Ele.Th (back elevation at thinnest), BAD (Belin/Ambrósio Enhanced Ectasia Display), and TBI (tomographic biomechanics index) proved to be highly effective with area under the curve (AUC) beyond 0.90. Stepwise logistic regression (SLR) model combination of corneal tomography and biomechanics of IHD, CBI, and TBI showed an excellent accuracy of AUC:0.999 for detecting keratoconus in FDR than using single MMI alone.

Conclusions: FDR with keratoconus indeed have an increased likelihood of developing corneal ectasia, including keratoconus itself. MMI screening of asymptomatic relatives can facilitate early stage or subclinical keratoconus detection.

Purpose: To evaluate the long-term visual, refractive, and tomographic outcomes of progressive thickness intrastromal corneal ring segment implantation using the KeraRing AS in patients with keratoconus (KC).

Methods: In this historical cohort study, 36 eyes from 36 patients with progressive KC underwent femtosecond-assisted KeraRing AS (Mediphaco, Brazil) implantation. Preoperative and postoperative uncorrected and corrected distance visual acuity, spherical equivalent (SE), astigmatism, keratometric indices, and pachymetric parameters were analyzed at 1- and 4-year follow-ups.

Results: Uncorrected distance visual acuity improved from 0.71 ± 0.36 to 0.34 ± 0.27 logarithm of the Minimum Angle of Resolution (logMAR) at 1 year and 0.28 ± 0.26 logMAR at 4 years (P <0.001). Corrected distance visual acuity improved from 0.33 ± 0.20 to 0.22 ± 0.16 logMAR at 1 year and 0.16 ± 0.13 logMAR at 4 years (P <0.001). SE improved from -5.38 ± 3.03 diopters (D) to -1.00 ± 1.48 D at 1 year but showed partial recurrence to -1.68 ± 1.83 D at 4 years (P = 0.011). Mean keratometry decreased from 46.52 ± 2.41 D to 43.82 ± 2.40 D at 1 year and increased significantly to 44.94 ± 2.18 D at 4 years (P <0.001). Corneal thickness parameters remained stable throughout the follow-up period.

Conclusions: KeraRing AS implantation provides significant initial improvements in visual and topographic parameters in progressive KC. However, notable regression occurs after 1 year, with significant increases in spherical power, SE, and all keratometric parameters between 1 and 4 years. This regression pattern emphasizes the importance of long-term monitoring and potential need for additional interventions.