Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial.

Limbal stem cell deficiency (LSCD) is a disease resulting from the loss or dysfunction of epithelial stem cells, which seriously impairs sight. Autologous limbal stem cell transplantation is effective in unilateral or partial bilateral disease but not applicable in total bilateral disease. An allogeneic source of transplantable cells for use in total bilateral disease can be obtained from culture of donated cadaveric corneal tissue. We performed a controlled multicenter study to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells in the treatment of bilateral LSCD. Patients were randomized to receive corneal epithelial stem cells cultured on amniotic membrane (AM): investigational medicinal product (IMP) or control AM only. Patients received systemic immunosuppression. Primary endpoints were safety and visual acuity, secondary endpoint was change in composite ocular surface score (OSS). Sixteen patients were treated and 13 patients completed all assessments. Safety was demonstrated and 9/13 patients had improved visual acuity scores at the end of the trial, with no significant differences between IMP and control groups. Patients in the IMP arm demonstrated significant, sustained improvement in OSS, whereas those in the control arm did not. Serum cytokine levels were measured during and after the period of immune suppression and we identified strongly elevated levels of CXCL8 in the serum of patients with aniridia, which persisted throughout the trial. This first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral LSCD demonstrates the feasibility and safety of this approach. Stem Cells Translational Medicine 2019;8:323-331.

Ocular response analyser to assess hysteresis and corneal resistance factor in low tension, open angle glaucoma and ocular hypertension.

PURPOSE: The aim of this study is to compare the hysteresis and corneal resistance factor (CRF) in normal tension glaucoma (NTG), primary open angle glaucoma (POAG) and ocular hypertension (OHT) eyes measured by the ocular response analyser (ORA). METHODS: This is a prospective, cross-sectional and comparative clinical trial. The setting was a teaching hospital in Birmingham, England. PATIENTS: 216 eyes with POAG, 68 eyes with NTG and 199 eyes with OHT. Observational procedures: Goldmann applanation tonometry and intraocular pressure (IOP), hysteresis and CRF measured by ORA and central corneal thickness (CCT) by ultrasonic pachymetery. The main outcome measures were IOP, CCT, hysteresis and CRF. RESULTS: The hysteresis in NTG, POAG and OHT eyes was 9.0 +/- 1.9, 9.9 +/- 2.1 and 10.2 +/- 2.0 mmHg; CRF was 9.1 +/- 2.2, 10.6 +/- 2.0 and 12.0 +/- 2.0 mmHg; IOP by Goldmann applanation tonometry and ORA was 14.7 +/- 2.8 and 15.3 +/- 4.2 mmHg, 16.7 +/- 4.0 and 16.9 +/- 4.6 mmHg and 20.5 +/- 4.1 and 20.0 +/- 4.5 mmHg; CCT was 526.5 +/- 42.2, 537.0 +/- 36.0 and 563.4 +/- 35.9 microm, respectively. The difference for CRF, IOP and CCT for NTG, POAG and OHT eyes was statistically significant. CONCLUSION: Hysteresis and CRF were highest in OHT eyes. These factors may prove to be useful measurements of ocular rigidity and may help to understand role of the corneal rigidity in monitoring the progress of conditions such as NTG, POAG and OHT.

Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes.

PURPOSE: To compare hysteresis, a novel measure of ocular rigidity (viscoelasticity) in normal and keratoconic eyes. METHODS: The study consisted of 207 normal and 93 keratoconic eyes. Eyes were diagnosed as keratoconic based on clinical examination and corneal topography. The hysteresis was measured by the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, NY). The data were recorded by Generation 3 software for the ORA. Central corneal thickness (CCT) was measured with a handheld ultrasonic pachymeter in the midpupillary axis. RESULTS: The mean hysteresis was 10.7 +/- 2.0 (SD) mm Hg (range, 6.1-17.6) in normal eyes compared with 9.6 +/- 2.2 mm Hg (range, 4.7-16.7) in keratoconic eyes. The difference was statistically significant (P < 0.0001, unpaired t-test). Mean CCT in the normal and keratoconic eyes was 545.0 +/- 36.4 microm (range, 471-650) and 491.8 +/- 54.7 microm (range, 341-611), respectively; the difference was significant (P < 0.0001, unpaired t-test). CONCLUSIONS: Hysteresis was significantly higher in normal than in keratoconic eyes. It may be a useful measurement in addition to CCT, when assessing ocular rigidity, and may be of particular importance when trying to correct intraocular measurements for increased or decreased ocular rigidity. Long-term studies of change in hysteresis may provide information on the progression of keratoconus.

Inadvertent Detachment of Descemet Membrane and Spontaneous Reattachment Following Cataract Surgery: An Anterior Segment Optical Coherence Tomography (AS OCT) Study.

Corneal oedema following cataract surgery during the immediate postoperative period is a common clinical problem, often due to endothelial injury due to multi-factorial mechanisms. Descemet's membrane detachment (DMD) is an underrecognized cause of postoperative corneal oedema. The understanding of the pathogenic mechanisms of DMD is still evolving. We report a case of DMD in a 64-year-old female presenting with immediate postoperative corneal oedema, diagnosed and monitored using anterior segment optical coherence tomography (AS OCT). Various mechanisms have been proposed for surgically induced DMD. We believe that hydration of surgical wounds at the end of surgery can inadvertently cause DMD, if DMD has not been recognized previously. Surgeons should be alert to this cause of DMD when hydrating surgical wounds.

Objective accommodative amplitude and dynamics with the 1CU accommodative intraocular lens.

PURPOSE: To compare the objective accommodative amplitude and dynamics of eyes implanted with the one-compartment-unit (1CU; HumanOptics AG, Erlangen, Germany) accommodative intraocular lenses (IOLs) with that measured subjectively. METHODS: Twenty eyes with a 1CU accommodative IOL implanted were refracted and distance and near acuity measured with a logMAR (logarithm of the minimum angle of resolution) chart. The objective accommodative stimulus-response curve for static targets between 0.17 and 4.00 D accommodative demand was measured with the SRW-5000 (Shin-Nippon Commerce Inc., Tokyo, Japan) and PowerRefractor (PlusOptiX, Nürnberg, Germany) autorefractors. Continuous objective recording of dynamic accommodation was measured with the SRW-5000, with the subject viewing a target moving from 0 to 2.50 D at 0.3 Hz through a Badal lens system. Wavefront aberrometry measures (Zywave; Bausch & Lomb, Rochester, NY) were made through undilated pupils. Subjective amplitude of accommodation was measured with the RAF (Royal Air Force accommodation and vergence measurement) rule. RESULTS: Four months after implantation best-corrected acuity was -0.01 +/- 0.16 logMAR at distance and 0.60 +/- 0.09 logMAR at near. Objectively, the static amplitude of accommodation was 0.72 +/- 0.38 D. The average dynamic amplitude of accommodation was 0.71 +/- 0.47 D, with a lag behind the target of 0.50 +/- 0.48 seconds. Aberrometry showed a decrease in power of the lens-eye combination from the center to the periphery in all subjects (on average, -0.38 +/- 0.28 D/mm). Subjective amplitude of accommodation was 2.24 +/- 0.42 D. Two years after 1CU implantation, refractive error and distance visual acuity remained relatively stable, but near visual acuity, and the subjective and objective amplitudes of accommodation decreased. CONCLUSIONS: The objective accommodating effects of the 1CU lens appear to be limited, although patients are able to track a moving target. Subjective and objective accommodation was reduced at the 2-year follow-up. The greater subjective amplitude of accommodation is likely to result from the eye's depth of focus of and the aspheric nature of the IOL.

Alcohol delamination of the corneal epithelium: an alternative in the management of recurrent corneal erosions.

PURPOSE: To investigate the efficacy of alcohol delamination in the management of recurrent corneal erosions (RCEs). DESIGN: Prospective single-center consecutive descriptive case series. PARTICIPANTS: Twelve patients with RCEs who did not respond to conservative management were treated with alcohol delamination. METHODS: A consecutive case series of 12 patients with RCEs who did not respond to conservative management were treated by alcohol delamination. A pain score was generated based on a visual analog scale of pain intensity. The duration of pain and frequency were also recorded. Patients were followed up at 1 week, 4 weeks, 3 months, 6 months, and 1 year and then at yearly intervals and monitored for recurrence of symptoms and corneal morphology. The removed epithelial sheet was examined by electron microscopy in 4 patients. INTERVENTION: The affected area of epithelium was peeled off after an application of 20% alcohol for 40 seconds under topical anesthesia. Eyes of patients were treated with an antibiotic and preservative-free artificial tear medication, and a bandage contact lens was inserted until epithelial healing was complete. MAIN OUTCOME MEASURES: Frequency of recurrence of erosions and duration and intensity of symptoms after alcohol delamination were studied. RESULTS: Eleven of the 12 eyes of patients had dramatic relief of symptoms over the follow-up period, ranging from 6 to 40 months. Eight patients were symptom free, and 1 patient had 2 mild symptom episodes in the first posttreatment month before becoming symptom free. The average follow-up period was 23.5 months. There were no residual effects from the application of alcohol noted in any patient. Electron microscopy of removed epithelium showed features of the underlying pathology. The separation of the epithelium occurred at the interface of the subepithelial abnormal deposit and the surface of Bowman's zone. CONCLUSION: Alcohol delamination appears to be a novel, simple, inexpensive treatment for RCEs. Unlike other methods, the removed epithelium is available as a sheet that may be subjected to further examination, though some of the changes observed may reflect the effect of alcohol on the epithelium.

The use of the Reichert ocular response analyser to establish the relationship between ocular hysteresis, corneal resistance factor and central corneal thickness in normal eyes.

PURPOSE: The aim of this study was to measure ocular hysteresis and corneal resistance factor (CRF), novel methods of analysing ocular rigidity/elasticity and to determine the relationship between central corneal thickness (CCT), hysteresis and CRF in normal subjects. DESIGN: Prospective, cross-sectional, clinical trial. PARTICIPANTS: The study included 207 normal eyes. METHODS: Hysteresis and CRF were measured by the ocular response analyser. The CCT was measured using a hand held ultrasonic pachymeter. MAIN OUTCOME MEASURES: Ocular hysteresis and CRF in normal patients and their relationship with CCT. RESULTS: The mean hysteresis was 10.7+/-2.0 mmHg standard deviation (S.D.) (range 6.1-17.6 mmHg); the mean CRF was 10.3+/-2.0 (range 5.7-17.1 mmHg). The mean CCT was 545.0+/-36.4 microm (471-650 microm). The relationship between hysteresis and CCT; CRF and CCT; CRF and hysteresis were significant (p<0.0001). CONCLUSION: This study demonstrated that corneal hysteresis increased with increasing CCT, however, the correlation was moderate. It would appear that CCT, hysteresis and CRF may measure different biomechanical aspects of ocular rigidity and are likely to be useful additional measurement to CCT in the assessment of ocular rigidity when measuring intraocular pressure (IOP). This may be of particular importance when trying to correct IOP measurements for increased or decreased ocular rigidity.

Collagen cross-linking treatment increases adhesion in mock corneal grafts.

PURPOSE: We tested the hypothesis that collagen cross-linking (CXL) could be used to promote adhesion in mock corneal grafts. METHODS: Donated human corneal tissue underwent epithelial debridement and was cut into sections measuring 4mm×3mm. Paired sections were sutured together with 10-0 vicryl, forming mock corneal grafts. Looped 6-0 sutures were placed at each end to facilitate tension measurement. Mock grafts underwent CXL before being cultured for 2days in Eagle's MEM culture medium. Control mock grafts did not undergo CXL treatment before culture. Tissue was obtained from 4 donors and a maximum of 2 controls and 2 treated grafts was obtained from each donor. Following the culture period, the 10-0 sutures were cut. The mock grafts were mounted on force transducers and were put under increasing tension until eventually the sections were pulled apart. RESULTS: The mean applied stress required to generate graft failure was calculated for all mock grafts±standard error of the mean. In the control group 0.236±0.09mPa of applied stress was required to cause graft failure, in comparison to 0.691±0.12mPa in the treated group. A paired t-test showed this result to be significant, (p=0.0087). CONCLUSION: The results of our study are consistent with our hypothesis that CXL treatment could be used to promote early adhesion between separate sections of corneal tissue.

Scotopic measurement of normal pupil size with the Colvard pupillometer and the Nidek auto-refractor.

PURPOSE: To compare prospectively, pupil size with the Nidek AR700A auto-refractor and the Colvard pupillometer. METHODS: Pupil diameter was measured in 46 eyes at 2 min intervals in a low mesopic and under photopic light conditions. RESULTS: The mean pupil diameter was 4.8+/-1.0mm with the Colvard pupillometer and 4.8+/-0.9mm with the Nidek auto-refractor in low mesopic light conditions. The mean photopic pupil diameter was 3.3+/-0.8mm with the Colvard pupillometer and 3.9+/-0.8mm with the Nidek auto-refractor. CONCLUSION: The pupil sizes are very similar with both instruments.

Aspheric ablation with the Nidek EC-5000 CX II with OPD-Scan objective analysis.

PURPOSE: To analyze the efficacy, predictability, stability, and safety of laser in situ keratomileusis (LASIK) to correct myopia and myopic astigmatism using the Nidek EC-5000 CX II laser and the Customized Aspheric Transition Zone (CATz) profile. METHODS: We conducted a retrospective analysis of 100 eyes (50 patients) with myopic astigmatism. A CATz profile was used in all eyes (profile 4) with an ablation zone of 5 mm and a transition zone of 9 mm, using Nidek FinalFit software. RESULTS: Average patient age was 39 years (range 21 to 69 yr). Preoperative mean spherical equivalent refraction was -4.70 +/- 2.53 D (range -11.88 to -0.50 D), mean preoperative sphere was -4.31 +/- 2.53 D (range -11.25 to -0.25 D), and mean preoperative cylinder was -0.78 +/- 0.69 D (range -3.25 to 0). Postoperative mean spherical equivalent refraction at 6 months was 0.12 +/- 0.53 D (range -1.63 to +0.88 D), mean postoperative sphere was 0.02 +/- 0.56 D (range -1.50 to +2.00 D), and mean postoperative cylinder was -0.29 +/- 0.50 D (range 0 to -1.75 D). Uncorrected visual acuity was 6/6 or better in 58% (58 eyes) and better than 6/12 in 93% (93 eyes). CONCLUSION: LASIK with the Nidek EC-5000 CX II laser and the CATz profile was effective, reasonably predictable, stable, and safe for correction of myopic astigmatism with a spherical component between -0.25 and -11.25 D, and a cylindrical component up to 3.25 D, using the techniques in this study. Astigmatism was undercorrected with the current algorithm.

Higher order aberrations with aspheric ablations using the Nidek EC-5000 CX II laser.

PURPOSE: To analyze the change in higher order aberrations in myopic and myopic astigmatic eyes following an aspheric ablation profile for laser in situ keratomileusis (LASIK) using a Nidek EC-5000 CX II excimer laser system. METHODS: We performed a retrospective audit of 38 eyes (19 patients) with myopia and myopic astigmatism. A customized aspheric transition zone profile (CATz) was used in all eyes (profile 4) with an ablation zone of 5 mm and a transition zone of 9 mm using FinalFit software and a Nidek EC-5000 CX II excimer laser system. RESULTS: Mean higher order aberrations (RMS) increased from 0.42 microm at baseline to 0.57 microm at 6-month follow-up. Mean spherical aberrations (Z12) increased from 0.02 microm at baseline to 0.33 microm after LASIK. Mean spherical aberration defocus equivalent (DEQ) increased from 0.56 microm at baseline to 1.54 at 6 months after surgery. Mean trefoil (Z6) was -0.11 microm at baseline and -0.14 microm at the 3-month examination. Mean coma (Z7) was -0.09 microm at baseline and -0.10 microm after surgery. Mean coma (Z8) was -0.03 at baseline and 0 at the 3-month examination. Mean trefoil (Z9) was -0.03 at baseline and -0.12 at the 3-month examination. CONCLUSION: The amount of postoperative higher order aberrations in these myopic eyes was acceptable. However, the clinical significance of these numerical changes in aberrations is not known.

Correlation of Nidek OPD-Scan objective refraction with subjective refraction.

PURPOSE: The aim of this study was to quantify how closely the Nidek OPD-Scan objective refraction correlated with subjective refraction. METHODS: A retrospective audit of the preoperative refraction of 80 myopic and myopic astigmatic eyes before laser in situ keratomileusis (LASIK) or laser supepithelial keratomileusis (LASEK) was performed. Objective refraction in the 5-mm zone was performed using a Nidek OPD-Scan. Subjective refraction was performed by a senior optometrist. Statistical analysis of sphere, cylinder, and spherical equivalent refraction measurements was then performed. RESULTS: Spherical measurements correlated well with a linear regression equation, with a correlation coefficient of 0.97. Cylinder measurements correlated less well, with a correlation coefficient of 0.85. Spherical equivalent refraction measurements correlated well, with a correlation coefficient of 0.97. Analyzing the numerical difference between each objective refraction and its corresponding subjective refraction, the majority of values were only 0.50 D apart for sphere, cylinder, and spherical equivalent refraction. CONCLUSION: There was good correlation between objective OPD-Scan and subjective refraction, especially for sphere and spherical equivalent refraction measurements, with regression gradients and correlation coefficients close to 1.

Nidek OPD-scan analysis of normal, keratoconic, and penetrating keratoplasty eyes.

PURPOSE: To determine by wavefront analysis the difference between eyes considered normal, eyes diagnosed with keratoconus, and eyes that have undergone penetrating keratoplasty METHODS: The Nidek OPD-Scan wavefront aberrometer was used to measure ocular aberrations out to the sixth Zernike order. One hundred and thirty eyes that were free of ocular pathology, 41 eyes diagnosed with keratoconus, and 8 eyes that had undergone penetrating keratoplasty were compared for differences in root mean square value. Three and five millimeter root mean square values of the refractive power aberrometry maps of the three classes of eyes were compared. Radially symmetric and irregular higher order aberration values were compared for differences in magnitude. RESULTS: Root mean square values were lower in eyes free of ocular pathology compared to eyes with keratoconus and eyes that had undergone penetrating keratoplasty. The aberrations were larger with the 5-mm pupil. Coma and spherical aberration values were lower in normal eyes. CONCLUSION: Wavefront aberrometry of normal, pathological, and eyes after surgery may help to explain the visual distortions encountered by patients. The ability to measure highly aberrated eyes allows an objective assessment of the optical consequences of ocular pathology and surgery. The Nidek OPD-Scan can be used in areas other than refractive surgery.

Surgical management of presbyopia.

Presbyopia is age-related reduction in amplitude of accommodation and the loss of the ability to change the eye's focus from far to near. It is the one of the most common age-related ailment. Traditional methods such as spectacle glasses or contact lenses are still the most widely used for correction of the problem. This article is an attempt to review the surgical options available for presbyopia.

Deep anterior lamellar keratoplasty: challenges in histopathological examination.

BACKGROUND/AIMS: To characterise histopathological changes in corneal buttons associated with deep anterior lamellar keratoplasty (DALK). METHODS: This was a retrospective, clinical laboratory study. All recipient corneal buttons that underwent DALK in the West of Scotland and were submitted to the regional Ocular Pathology Laboratory (Glasgow, UK) between 2001 and 2010 were examined. Cases affected by artefacts secondary to DALK were highlighted. Keratoconus cases that underwent DALK were compared to those that underwent penetrating keratoplasty (PK). RESULTS: 225 DALK corneal buttons were examined. Of these, 61.8% were affected by artefacts or problems related to DALK. Overall, 58.2% of the affected buttons were affected by corneal emphysema related to intrastromal air injection (the 'big bubble' technique), 5.3% by epithelial oedema related to the hydrodelamination procedure, which mimicked bullous keratopathy secondary to endothelial cell deficiency, and 0.9% were lost specimens. We were not able to identify any conus, which is a characteristic histopathological feature of keratoconus, in 10 (7.4%) of the DALK-keratoconus cases as opposed to two (1.6%) of the PK-keratoconus cases (p=0.036). CONCLUSIONS: DALK poses new challenges for histopathological examination of corneal buttons. Awareness of DALK-related histopathological characteristics should be raised among ocular pathologists and ophthalmologists in view of the increasing popularity of this technique.

Delayed dislocation of an injectable hydrophilic acrylic lens after Nd:YAG capsulotomy in anterior capsular contraction syndrome.

Posterior dislocation of IOLs has been reported following Nd:YAG laser for anterior capsule contraction in only 3 cases and these involved plate haptic silicone lenses; while the dislocation of IOLs into the vitreous cavity following posterior Nd:YAG laser capsulotomy have been reported in plate haptic silicone lenses and single piece hydrophilic acrylic (polymacon) lenses. We report a patient who suffered the delayed dislocation of an injectable hydrophilic acylic IOL (SlimFlex-m 123 IOL, PhysIOL, Liège, Belgium) following combined Nd:YAG laser anterior and posterior capsulotomy. We also explore the factors that may predispose to anterior capsular contraction syndrome and IOL dislocation.

Combined amniotic membrane transplant and anterior stromal puncture in painful bullous keratopathy: clinical outcome and confocal microscopy.

OBJECTIVE: To report the outcomes of anterior stromal micropuncture (ASP) combined with amniotic membrane transplantation (AMT) in the management of painful bullous keratopathy (BK) with poor visual potential, and to assess amniotic membrane (AM) retention. DESIGN: Case series, retrospective review. PARTICIPANTS: Twelve eyes of 12 patients with BK causing intractable pain or discomfort and poor visual potential, treated between March 2006 and October 2008 at Gartnavel General Hospital, Glasgow. METHODS: Epithelial debridement was followed by ASP and the amniotic membrane was stabilized with a purse-string 10/0 nylon corneal suture and a bandage contact lens. During a mean follow-up of 67 weeks (range, 27-139 weeks), pain relief, epithelial healing, visual changes, confocal microscopy, and appearance of new bullae were evaluated. Success was defined as complete resolution or significant improvement in pain. RESULTS: Twelve eyes of 12 patients, mean age 61 years (range, 40-88 years), were identified. Corneal epithelial healing was complete in 11 eyes 1 month postoperatively. Pain and conjunctival inflammation resolved in 11 patients (91.67%) and improved from severe to mild in the remaining patient. Incorporation of the AMT was observed on slit-lamp biomicroscopy in all eyes and was confirmed using confocal microscopy at final follow-up. CONCLUSIONS: ASP combined with AMT is safe and effective, alleviates pain and discomfort, reduces ocular inflammation, and promotes epithelial healing and resolution of bullae in patients with BK with poor visual potential. There was long-term evidence of amniotic membrane graft retention in all eyes after the procedure, suggesting that ASP may improve the long-term retention rate of AM.