Belgian Endothelial Surgical Transplant of the Cornea (BEST cornea) protocol: clinical and patient-reported outcomes of Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK) - a multicentric, randomised, parallel group pragmatic trial in corneal endothelial decompensation.

OBJECTIVES: Corneal blindness is the third most frequent cause of blindness globally. Damage to the corneal endothelium is a leading indication for corneal transplantation, which is typically performed by lamellar endothelial keratoplasty. There are two conventional surgical techniques: Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK). The purpose of this study is to compare both techniques. METHODS AND ANALYSIS: The trial compares UT-DSAEK and DMEK in terms of clinical and patient reported outcomes using a pragmatic, parallel, multicentric, randomised controlled trial with 1:1 allocation with a sample size of 220 participants across 11 surgical centres. The primary outcome is the change in best-corrected visual acuity at 12 months. Secondary outcomes include corrected and uncorrected vision, refraction, proportion of high vision, quality of life (EQ-5D-5L and VFQ25), endothelial cell counts and corneal thickness at 3, 6 and 12 months follow-up appointments. Adverse events will also be compared 12 months postoperatively. ETHICS AND DISSEMINATION: The protocol was reviewed by ethical committees of 11 participating centres with the sponsor centre issuing the final definitive approval. The results will be disseminated at clinical conferences, by patient partner groups and open access in peer-reviewed journals. GOVERNANCE OF THE TRIAL: Both, trial management group and trial steering committee, are installed with representatives of all stakeholders involved including surgeons, corneal bankers, patients and external experts. TRIAL REGISTRATION NUMBER: NCT05436665.

Diagnostic patterns in keratoconus.

PURPOSE: To investigate the current patterns of diagnosis and referral in keratoconus. METHODS: A retrospective chart review was performed of patients who had recently been diagnosed with keratoconus and attended dedicated clinics at Antwerp University Hospital, Belgium and Maria Middelares General Hospital, Ghent, Belgium between June 2013 and February 2018. Exclusion criteria included longstanding keratoconus diagnosis, reduced cognitive capabilities and prior surgical procedures (corneal crosslinking, penetrating keratoplasty or any type of refractive surgery). RESULTS: Three-hundred and ninety-nine patients (722 eyes) were included in this study. The mean age was 24.7 ± 6.5 years and the average maximal keratometry was 51 ± 5.2 D for the better eye and 58.4 ± 9.6 D for the worse eye. Upon diagnosis, 233 eyes (32.2 %) and 51 eyes (7.1 %) had a thinnest pachymetry <450 and <400 µm, respectively. At 6-month follow-up, 58 % of patients had been fitted with specialty contact lenses. During follow-up, 199 eyes (27.6 %) underwent corneal crosslinking. One patient underwent corneal graft surgery of his worse eye due to contact lens intolerance and insufficient visual acuity. CONCLUSION: Despite advances in diagnostic tools, keratoconus is often diagnosed at a relatively late stage. Earlier detection of keratoconus would increase the overall clinical benefit of corneal crosslinking. Further research into screening strategies is required to develop cost-effective screening programs.

Mini-Scleral Lenses Improve Vision-Related Quality of Life in Keratoconus.

PURPOSE: To evaluate the effects of mini-scleral lenses on visual acuity (VA) and visual functioning in patients with keratoconus. METHODS: This prospective, interventional study examined the effects of mini-scleral lenses on VA and visual functioning in patients with keratoconus. Patients younger than 18 years or with a history of refractive surgery or corneal graft surgery were excluded. Patients were fitted with mini-Misa lenses, Senso mini-scleral lenses, or Zenlens mini-scleral lenses. Outcome measures were scleral lens-corrected VA and vision-related quality of life as assessed with the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-39). RESULTS: Eighty-nine eyes of 50 keratoconus patients were included in the study. Median baseline logarithm of the minimal angle of resolution VA with habitual correction was 0.22 (range 0.02-1.04). Mini-scleral lens fitting resulted in a statistically significant visual improvement (median 0; P < 0.0001). At the 6-month follow-up, 11 patients (22%) had abandoned mini-scleral lens wear, primarily because of difficulties with lens handling (7 patients). Of the 39 patients with continued wear, 33 patients (84.6%) wore their lenses for a daily average of 12 hours. NEI-VFQ scoring in these patients showed significantly improved results for both visual functioning and socioemotional scales after scleral lens fitting (P < 0.0001). CONCLUSIONS: Mini-scleral lenses significantly improve VA and visual functioning on NEI-VFQ in patients with keratoconus. Difficulties with lens insertion and removal are the principal reason for lens dropout.

Repeatability of the Pentacam HR in Various Grades of Keratoconus.

PURPOSE: To evaluate the repeatability of an extensive number of relevant indices with the Pentacam HR in keratoconus of varying severity and normal eyes. DESIGN: Reliability analysis. METHODS: This study was performed at Antwerp University Hospital, Belgium, and enrolled 20 healthy volunteers (20 eyes) and 69 patients (69 eyes) with keratoconus. Three consecutive measurements were performed by the same operator with Pentacam HR in keratoconus and normal eyes. Exclusion criteria included past ocular surgery, recent rigid contact lens wear, and corneal scarring. The keratoconus group was subdivided according to the Belin/Ambrosio total deviation value: subclinical, mild, and moderate. The within-subject standard deviation and repeatability limit were computed for repeatability assessment. The tolerance index (TI) was calculated to compare across parameters with different measurement scales. For the sample size included, TI > 0.36 signified statistical significance at the 0.05 level. RESULTS: Repeatability in subclinical keratoconus did not differ significantly from controls (P > .05), except for wavefront aberrations. In mild keratoconus, 11 of 18 (61.1%) anterior corneal, 7 of 14 (50%) posterior corneal, 2 of 5 (40%) pachymetry, 7 of 11 (63.6%) combined, and 1 of 6 (16.7%) densitometry parameters showed significantly worse repeatability compared to controls (TI > 0.36). Repeatability of most parameters worsened in moderate disease. In particular, maximal keratometry and anterior astigmatism showed significantly worse repeatability in moderate keratoconus. CONCLUSIONS: Measurement variability of Pentacam HR is of clinical relevance when assessing for progression of keratoconus. We provide reference repeatability values and scale independent analysis of relevant corneal parameters in keratoconus of varying degrees.

The Outcome of Scleral Lens Fitting for Keratoconus With Resolved Corneal Hydrops.

PURPOSE: To investigate the success and failure of scleral lens fitting in patients with keratoconus with resolved hydrops. METHODS: Retrospective case series of patients with keratoconus who attended the Ophthalmology Department at Antwerp University Hospital, Belgium, and developed acute hydrops between January 1, 2015, and June 30, 2018. The exclusion criteria included amblyopia, mental retardation, and insufficient follow-up. RESULTS: Of the 25 patients with keratoconus with acute hydrops, 14 patients (16 eyes) were included in this study. Median age was 31 years (range 19-52 years). Before hydrops, the median maximum keratometry value of affected eyes was 81.3 D (range 66.3-108.3 D). Acute hydrops was managed medically in 5 eyes (31.3%), by observation in 5 eyes (31.3%), by application of bandage contact lens in 1 eye (6.3%), and compression corneal sutures in 5 eyes (31.3%). Contact lens fitting after hydrops was not necessary for 2 patients (2 eyes; 12.5%) because of excellent vision in the fellow eye. Of the remaining patients, 11 (68.8%) were successfully fitted with mini-scleral lenses, with a median visual acuity of 0.7 (0.5-0.9; decimal Snellen). Three patients (3 eyes; 18.8%) proceeded to graft surgery because of limited visual acuity with scleral lenses (n = 2) or persistent edema (n = 1). CONCLUSIONS: Scleral lenses are effective for providing satisfactory visual acuity after corneal hydrops in keratoconus. A scleral lens trial is advised before listing patients for graft surgery.

A multilevel analysis of factors influencing the flow efficiency of the cataract surgery process in hospitals.

PURPOSE: To detect factors contributing to variation in cataract surgery processes. METHODS: A multilevel study was conducted to compare the process of cataract surgery between hospitals in Belgium. The main data were collected through non-participative observations and time measurements in four hospitals. Surgeons (n = 16) performing cataract surgery in the selected region and their patients (n = 274) undergoing cataract surgery were observed. Flow efficiency is measured in the operating room (OR) as time for preparation, surgery, exit and turnover. RESULTS: Flow efficiency in the OR can be negatively influenced by the severity of the cataract [+2.778 (1.139) min in preparation time (p < 0.05); +4.616 (1.786) min in surgery time when severe cataract (p < 0.05)] and the presence of special-cause variation [+2.832 (1.893) min preparation time (p < 0.05); +2.503 (1.277) min surgery time (p < 0.05); +1.181 (0.350) min exit time (p ≤ 0.001)]. Administering topical analgesia instead of peribulbar [+13.548 (4.436) min preparation time (p ≤ 0.001)], retrobulbar [+3.856 (1.548) min surgery time (p ≤ 0.05)] or general analgesia [+5.617 (2.536) min surgery time (p < 0.05); +5.175 (0.817) min exit time (p ≤ 0.001)] enhances flow efficiency. The experience of surgeons (>15 years) impacts flow efficiency [+12.838 (5.922) min surgery time when low experience]. The volume of cataracts performed annually per surgeon did not have a significant impact on flow efficiency. The use of specialized scrub nurses [-7.146 (3.099) min preparation time (p ≤ 0.05); -2.116 (0.586) min turnover time (p ≤ 0.05)] and the eye clinic design [-1.742 (0.686) min exit time (p < 0.05); 2.296 (1.034) min turnover time (p ≤ 0.05)] benefit flow efficiency. CONCLUSION: Controllable and uncontrollable factors with clinical and organizational causes influencing flow efficiency in the cataract process were found. These factors can be taken into account in the management of the healthcare process.

Confocal microscopy of corneal crystals in a patient with hereditary tyrosinemia type I, treated with NTBC.

PURPOSE: To describe the confocal microscopic findings in a patient with hereditary tyrosinemia type I (HT-I) treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) who developed corneal crystals. METHODS: In this case study, we describe the confocal microscopic findings in a boy, who was diagnosed with HT-I at the age of 4 months. At 16 years of age, he developed painful corneal lesions in both eyes. On slit-lamp examination, whorl-like branching epithelial corneal lesions were found, staining faintly with fluorescein. His NTBC treatment was stopped and reintroduced at a lower dose after 1 month. The lesions clearly regressed, leaving only mild residual epithelial scarring, without fluorescein staining and without pain. Confocal microscopy was performed in the acute painful stage and in the asymptomatic convalescent stage 5 months later. RESULTS: Confocal microscopy confirmed the presence of slender birefringent spiky crystals in the very superficial corneal epithelium. In the asymptomatic convalescent phase, the crystals clearly persisted on confocal microscopy, although they were barely visible on slit-lamp examination. CONCLUSIONS: This is the first in vivo demonstration by confocal microscopy of corneal crystals present in a patient with proven type I tyrosinemia, under NTBC treatment.

Restrictive extraocular myopathy: a presenting feature of acromegaly.

A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI) of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT) of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

Increased levator muscle function by supramaximal resection in patients with blepharophimosis-ptosis-epicanthus inversus syndrome.

OBJECTIVE: To study the efficacy and clinical and anatomical results of supramaximal levator resection in patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) with severe congenital ptosis with poor levator function (LF). METHODS: Eleven patients with molecularly proven BPES underwent supramaximal levator resection. Palpebral fissure height and LF were measured preoperatively and postoperatively. RESULTS: All patients showed an excellent reduction in ptosis with a single intervention resulting in a clear visual axis. Palpebral fissure height improved from mean (SD) 3.3 (0.7) mm preoperatively to 7.1 (0.9) mm postoperatively (P value <.001). Four patients underwent additional surgery because of cosmetic issues with eyelid height asymmetry. All patients showed a marked, consistent, and lasting improvement in LF, going from mean (SD) 1.9 (0.9) mm preoperatively to 7.4 (1.1) mm postoperatively (P value <.001). This improvement could be attributed to the presence of a very long and thin tendon, as well as a striated muscle belly. This elongated aponeurosis inhibits the levator muscle from having sufficient impact on the vertical eyelid excursion. CONCLUSIONS: We demonstrated that supramaximal levator resection performed in patients with BPES not only results in good cosmetic appearance in terms of ptosis reduction in the majority of cases but also in a significant increase of the levator palpebrae superioris function. An anatomical substrate was found to explain these findings. To our knowledge, this is the first study to provide evidence of a marked increase in LF in BPES due to resection of the elongated tendon with reinsertion of the muscle belly.

Correction of the lower eyelid malpositioning in the blepharophimosis-ptosis-epicanthus inversus syndrome.

PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant complex eyelid malformation. The authors aim to offer an explanation for the lower eyelid malformation and propose a novel surgical approach to correct it. METHODS: An observational and interventional case series of 10 consecutive, molecularly proven BPES patients who underwent surgical repair of the lower eyelid malformation. During surgery detailed anatomical examination and surgical repositioning of the medial canthal tendon was performed. All the patients were followed up regularly after the surgery and assessed for epiphora. RESULTS: All patients exhibited a marked asymmetry in the attachment of the lower and upper eyelid to the medial canthal tendon, with the lower eyelid being much less attached. This resulted in an abnormal downward concavity with a temporal ectropion and a temporally displaced lower eyelid. Consequently, the inferior punctum was displaced temporally. All patients underwent a novel surgical technique to remediate this, namely, inserting a 4.0 nylon suture between the tarsal plate of the lower eyelid and the medial canthal tendon during telecanthus surgery. This simple additional surgical step corrected not only the position of the lower eyelid but also its abnormal downward concavity, the temporal ectropion and the lateral displacement of the inferior punctum. None of the authors' patients had lasting epiphora. CONCLUSION: Lateral displacement of the inferior punctum is an important hallmark in the diagnosis of BPES. The authors demonstrate an anatomical explanation for the complex lower eyelid malformation and also propose a novel surgical technique to correct this. During surgical repair of the telecanthus and blepharophimosis, specific attention should be paid to reattachment of the lower eyelid to the medial canthal tendon. This understanding improves clinical diagnosis and surgical treatment of BPES patients.

Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy.

AIMS: To determine the accuracy of diagnosing microbial keratitis by masked medical and non-medical observers using the Heidelberg Retina Tomograph II/Rostock Cornea Module in vivo confocal microscope. METHODS: Confocal images were selected for 62 eyes with culture- or biopsy-proven infections. The cases comprised 26 Acanthamoeba, 12 fungus, three Microsporidia, two Nocardia and 19 bacterial infections (controls). The reference standard for comparison was a positive tissue diagnosis. These images were assessed on two separate occasions by four observers who were masked to the tissue diagnosis. Diagnostic accuracy indices, kappa statistic and percentage agreement values were calculated. The Spearman correlation coefficient (r(s)) was calculated for the number of correct diagnoses versus duration of disease. RESULTS: The highest sensitivity and specificity values were 55.8% and 84.2%, respectively, and the lowest sensitivity and specificity values were 27.9% and 42.1%, respectively. The highest positive and lowest negative likelihood ratios were 2.94 and 0.59, respectively. Agreement values were: fair to moderate (kappa 0.22-0.44) for reference standard versus observer diagnosis, moderate to good in intraobserver variability (repeatability, kappa 0.56-0.88) and poor to moderate in interobserver variability (reproducibility, kappa 0.15-0.47). The correct diagnosis was associated with duration of disease for Acanthamoeba keratitis (r(s)=0.60, p=0.001). CONCLUSIONS: The diagnostic accuracy of microbial keratitis by confocal microscopy is dependent on observer experience. Intraobserver repeatability was better than interobserver reproducibility. Difficulty in distinguishing host cells from pathogenic organisms limits the value of confocal microscopy as a stand-alone tool in diagnosing microbial keratitis.

Orbital cellulitis as complication of endophthalmitis after cataract surgery.

A 74-year-old man presented with light perception and presumed early bacterial endophthalmitis in the left eye after cataract surgery. Vitreous tap biopsy and core vitrectomy were performed immediately, along with injection of antibiotic agents (ceftazidime and vancomycin). Culture of the vitreous tap revealed Pseudomonas aeruginosa sensitive to ceftazidime. The eye remained inflamed despite 2 additional intravitreal ceftazidime injections. Orbital cellulitis with perforation of the globe was suspected and confirmed on magnetic resonance imaging, and enucleation was performed. Endophthalmitis due to P aeruginosa is associated with poor visual outcomes despite prompt treatment with appropriate intravitreal antibiotic agents. Progression to orbital cellulitis in immunocompetent patients is extremely rare. Careful monitoring of patients with endophthalmitis after cataract surgery is recommended. .

Inverted papilloma arising primarily from the lacrimal sac.

A 24-year-old female was referred with epiphora and a non-tender swelling within the right lacrimal fossa, present for 6 months. There were no previous episodes of dacryocystitis. Computed tomography showed a homogenous mass within the lacrimal fossa without contrast enhancement. Pathology following resection of the whole lacimal sac revealed the presence of an inverted papilloma (IP) with a sharp transition between the papilloma and the normal lacrimal duct epithelium. In situ hybridisation was positive for low risk HPV subtypes. An IP is a benign but infiltrative epithelial neoplasm with malignant potential characterised by a high recurrence rate. Majority of cases arise from the nasal wall and paranasal sinuses. In this case report, we demonstrate an IP confined to the lacrimal sac with clear-cut pathology proof, which implicates the lacrimal sac as a primary site of origin.

Ectopic meningioma anterior to the lacrimal gland fossa.

A 66-year-old man reported a slowly growing tumor on the lateral edge of his left upper eyelid. This lesion was hard but movable on palpation. A neoplasm of the lacrimal gland was suspected. CT showed a highly calcified lesion at the left upper eyelid. Resection of the tumor was performed, which was located just behind the orbital septum and in front of the lacrimal gland. Anatomopathologic investigation of the excised specimen with immunohistochemistry revealed a benign meningioma of a meningotheliomatous type, containing multiple bone elements. An ectopic orbital meningioma is rare, and this is the first case of a unique lateral localization of this lesion. Therefore, it should be included in the differential diagnosis of a lacrimal gland tumor.

Eye bank issues: II. Preservation techniques: warm versus cold storage.

Most of the tissue used for penetrating keratoplasty is issued through eye banks that store the corneoscleral button either in hypothermic storage at 2-6 degrees C or in organ culture at 31-37 degrees C. These two preservation techniques differ in technical aspects, tissue evaluation possibilities, storage time and microbiological safety. Hypothermic storage is simple and requires little expensive equipment. In general a pre-storage evaluation of the endothelium is performed by specular microscopy and storage time is usually around 7-10 days. Organ culture is a relatively complicated technique requiring more expertise and well-equipped facilities. Evaluation of the endothelium is not only performed before storage, but is routinely performed after storage through the use of light microscopy. With organ culture the allowed storage period is longer, up to four weeks. The vulnerability of organ culture to microbial contamination can be turned into an advantage because it allows the detection of residual micro-organisms on the cornea before surgery. Both preservation techniques seem to result in similar graft survival. The method of choice for preservation of the donor cornea is dictated by a number of factors mentioned in this review and this helps to explain the geographical differences in the use of the different techniques.

Role of natural killer cells in the rejection process of corneal allografts in rats.

BACKGROUND: The exact mechanism of human corneal allograft rejection, which is the major cause of corneal transplant failure, remains unclear. We investigated the role of natural killer (NK) cells in rat corneal allograft rejection by examining the aqueous humor (AH) cell infiltrate on different postoperative days. METHODS: Flow cytometric analysis was performed on the AH and submandibular draining lymph node (DLN) cells before transplantation and at different time points thereafter. In addition, we performed functional cytotoxicity assays with cells present in the AH during corneal rejection. RESULTS: We demonstrated a gradual increase in the absolute cell number of different hematopoietic subpopulations in the AH after allogeneic cornea transplantation. CD3CD4 cells, mainly monocytes and macrophages, were the predominant subpopulation 2 days after transplantation, followed by a successive relative increase of CD4 T cells, CD8 T cells, CD161 T cells, and NK cells. NK and CD161 T cells were present at a 10- to 15-fold higher percentage than in the DLN, suggestive of local expansion of these cells. A higher percentage of NK cells were CD8-negative compared with DLN NK cells. AH cells specifically lysed allogeneic cells, and this cytotoxicity was mainly attributable to NK cells but not to CD4 or CD8 T lymphocytes. CONCLUSION: These results confirm the crucial role of CD4 cells in the allogeneic corneal graft rejection process and implicate NK cells as possible mediators of the rejection.

Therapeutic penetrating keratoplasty: clinical outcome and evolution of endothelial cell density.

PURPOSE: To identify the influence of the underlying etiology on the outcome of therapeutic penetrating keratoplasty (PKP) in the management of corneal perforation, impending perforation or refractory corneal disease. METHODS: A retrospective observational case series with 28 patients (28 eyes) was performed. Patients were divided in two subgroups, based on the underlying ocular disease leading to the therapeutic PKP. Group I consisted of 15 patients (54%) with an infectious etiology, the other 13 patients (46%) with a noninfectious condition belonged to group II. Mean follow up was 23.2 months (median 21 months). RESULTS: An enucleation could be avoided in all but two cases. In group I, 12 of 15 (80%) grafts remained clear, compared with only 3 of 13 (23%) in group II (p = 0.0004). Visual acuity (VA) amelioration was achieved in 20 of 28 patients (71%). In group I the postoperative VA was significantly better than preoperatively (p = 0.002); however, in group II the improvement was only borderline significant (p = 0.05). Overall five out of ten (50%) patients with a therapeutic PKP in group I had an endothelial cell density >or= 1900 cells/mm2 at the time of their last specular microscopy. CONCLUSION: Our study demonstrates the importance of underlying etiology on the outcome of therapeutic PKP. Graft survival and postoperative visual acuity varied widely depending on the underlying ocular disease, and it was clear that therapeutic PKP has a much better prognosis in infectious conditions when compared with noninfectious conditions. We believe that these good results can justify the use of therapeutic PKP in selected cases of infectious keratitis.