Christina N Grupcheva

Assessing the sub-basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy.

The purpose of the study was to perform quantitative analysis of the sub‐basal epithelial nerve plexus of healthy, living human cornea, using real time in vivo confocal microscopy and the analySIS software system. The study was based on in vivo confocal microstructural analysis of 50 eyes of 50 subjects, divided into two age groups: group 1 (n = 25) 25 ± 5 years of age, and group 2 (n = 25) 70 ± 5 years of age. All subjects exhibited clinically healthy corneas. The overall nerve density was 632.35 ± 287.57 µm/mm2 for group 1 and 582.39 ± 327.13 µm/mm2 for group 2. The mean fibre diameter was measured at 0.52 ± 0.23 µm for group 1 and at 0.56 ± 0.27 µm for group 2. Beadings of the nerve fibres were recorded at a density of 213 ± 123/mm for group 1 and 201 ± 192/mm for group 2. Establishing standards for normal nerve density and morphology of the living human cornea at different ages may be beneficial, both in early detection and follow up of various corneal diseases and in post‐surgical management following corneal surgery.

The Auckland Cataract Study: co-morbidity, surgical techniques, and clinical outcomes in a public hospital service

Aim: To prospectively assess cataract surgery in a major New Zealand public hospital by defining presenting clinical parameters and surgical and clinical outcomes in a cohort of subjects just below threshold for treatment, based upon a points based prioritisation system. Methods: The prospective observational study comprised 488 eyes of 480 subjects undergoing consecutive cataract operations at Auckland Hospital. All subjects underwent extensive ophthalmic examination before and after surgery. Details of the surgical procedure, including any intraoperative difficulties or complications, were documented. Postoperative review was performed at 1 day and 4 weeks after surgery. Demographic data, clinical outcomes, and adverse events were correlated by an independent assessor. Results: The mean age at surgery was 74.9 (SD 9.6) years with a female predominance (62%). Significant systemic disease affected 80% of subjects, with 20% of the overall cohort exhibiting diabetes mellitus. 26% of eyes exhibited coexisting ocular disease and in 7.6% this affected best spectacle corrected visual acuity (BSCVA). A mean spherical equivalent of −0.49 (1.03) D and mean BSCVA of 0.9 (0.6) log MAR units (Snellen equivalent approximately 6/48) was noted preoperatively. Local anaesthesia was employed in 99.8% of subjects (94.9% sub-Tenons). The majority of procedures (97.3%) were small incision phacoemulsification with foldable lens implant. Complications included: 4.9% posterior capsule tears, 3.8% cystoid macular oedema, and one case (0.2%) of endophthalmitis. Mean BSCVA after surgery was 0.1 (0.2) log MAR units (6/7.5 Snellen equivalent), with a mean spherical equivalent of −0.46 (0.89) D, and was 6/12 or better in 88% of all eyes. A drop in BSCVA, thought to be directly attributable to the surgical intervention, was recorded in a small percentage of eyes (1.5%) after surgery. Conclusion: This study provides a representative assessment of the management of cataract in the New Zealand public hospital system. A predominantly elderly, female population, frequently exhibiting significant systemic illness and coexisting ocular disease, relatively advanced cataracts, and poor BSCVA, presented for cataract surgery. The majority of subjects underwent small incision, phacoemulsification, day case surgery. While almost 90% achieved at least 6/12 BSCVA post-surgery, approximately 5% sustained an adverse intraoperative event and 1.5% of eyes exhibited a reduction in BSCVA postoperatively.

Differential diagnosis of corneal oedema assisted by in vivo confocal microscopy

The purpose of this study was to demonstrate microstructural differences between clinically similar, but aetiologically different, cases of corneal oedema in four subjects. In vivo confocal microscopy highlighted oedema of the basal epithelium, prominent nerve–keratocyte interactions, and typical ‘epithelialization’ of the endothelium in a case of iridocorneal endothelial syndrome; however, a similar microstructural appearance was observed in a case of presumed herpetic disciform keratitis. The latter diagnosis was subsequently revised on this basis. Confocal examination of Fuchs’ endothelial dystrophy demonstrated oedema of the basal epithelium, prominent wing cells, anterior stromal alterations, fibrosis of Descemet’s membrane and a typical ‘strawberry’ appearance of the endothelium. In contrast, in vivo microstructural examination of bilateral keratoconus with hydrops confirmed oedema mainly involving the epithelium and anterior stroma. In vivo confocal microscopy allows the clinician to observe the living cornea at a microstructural level and to better diagnose and differentiate borderline or unusual cases of corneal oedema.

In vivo confocal microscopy of posterior polymorphous dystrophy.

Purpose: This study was designed to delineate the morphologic features of posterior polymorphous dystrophy (PPD) using in vivo confocal microscopy. Methods: Six patients with clinically diagnosed PPD were examined by slit-lamp biomicroscopy, Orbscan II slit-scanning elevation topography, and in vivo confocal microscopy. Results: Endothelial cell densities ranged from 613 to 3,405 cells/mm2 and endothelial polymegathism was noted in all cases, whereas endothelial pleomorphism was not a prominent feature. Three cases exhibited bright endothelial nuclei. A variety of abnormal curvilinear and vesicular abnormalities were imaged by in vivo confocal microscopy, with lesions ranging between 6 and 159 μm in diameter. Abnormal endothelial cells were visible within some of these lesions. Six cases showed hyperreflectivity at the level of Descemets membrane around the lesions. Deep stromal keratocytes appeared to aggregate around, or were compressed by, the endothelial lesions in one case. Conclusions: We report the largest case series of PPD imaged by in vivo confocal microscopy. The ability of in vivo confocal microscopy to assess the living cornea over time enables monitoring of disease progression and thus the potential to identify and correlate development of, or changes in, microstructural features. As more data become available, these analyses may enable the formulation of prognostic and diagnostic criteria.

Imaging posterior polymorphous corneal dystrophy by in vivo confocal microscopy

To identify features of posterior polymorphous dystrophy (PPMD) by in vivo confocal microscopy, the corneas of a female patient with PPMD were examined using slit‐lamp biomicroscopy and slit‐scanning in vivo confocal microscopy. Characteristic endothelial vesicular and band lesions were seen clinically and easily identified using in vivo confocal microscopy. However, endothelial pleomorphism, an increased density and reflectance of posterior stromal keratocytes, and prominence of corneal nerves were also delineated. In vivo confocal microscopy enhances clinicopathological diagnosis and follow up of corneal dystrophies with subtle clinical presentations, such as PPMD.

Improved corneal wound healing through modulation of gap junction communication using connexin43-specific antisense oligodeoxynucleotides.

PURPOSE Gap junctions play a major role in corneal wound healing. This study used reproducible models of corneal wound healing to evaluate the effect of a gap junction channel modulator, connexin43 (Cx43) antisense oligodeoxynucleotides (AsODN), on corneal healing dynamics. METHODS A mechanical scrape wound model was used to evaluate Cx43 AsODN penetration and initial wound reepithelialization 12 hours postsurgery. Thereafter, detailed analyses of corneal edema, inflammation, and healing were performed in an excimer laser surface ablation model. In vivo confocal microscopy determined clinical parameters (edema, haze) and cellular changes (stromal hypercellularity, reepithelialization), whereas histology and immunohistochemistry were used to quantify stromal edema, inflammation, and reepithelialization. RESULTS Cx43 AsODN penetrated through the hydrophilic stroma where the epithelium had been removed and accumulated in the basal epithelium close to the wound edge. Twelve hours after scrape wounding, Cx43 AsODN-treated eyes showed a significant reduction in wound area compared with the vehicle alone (1.59±0.37 and 2.29±0.58 mm2, respectively, P<0.01). After excimer laser ablation, stromal edema and inflammation were reduced, with endothelial structures being clearly visible, and reepithelialization rates were again increased in Cx43 AsODN-treated eyes. Histologic analysis confirmed reduced edema in the central wound site and at the periphery of treated corneas (P<0.05), whereas immunohistochemistry showed lower Cx43 levels (P<0.05), reduced myofibroblast activation, and improved epithelial basal lamina deposition in antisense-treated wounds (P<0.01). CONCLUSIONS Application of Cx43 AsODN to the cornea reduces stromal edema and inflammation, promoting faster wound closure and a more uniform repair of the epithelial basal lamina after laser ablation.

The Auckland Cataract Study: 2 year postoperative assessment of aspects of clinical, visual, corneal topographic and satisfaction outcomes

Aim: To assess clinical, visual, computerised corneal topographic, and subjective satisfaction with visual acuity, in a cohort of subjects 2 years after phacoemulsification surgery in a public hospital in New Zealand. Methods: Prospective study of a representative sample of 97 subjects (20%) randomly selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort. The clinical assessment protocol was identical to the ACS and included an extensive questionnaire to enable direct comparisons to be made between the two groups. Results: The study population was predominantly female (66%) with a mean age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and 10.3% of subjects respectively, and 10.3% required referral to either a general practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with mean spherical equivalent −0.37 (1.01) dioptres (D) and astigmatism −1.07 (0.70) D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5 Snellen equivalent), spherical equivalent −0.59 (1.07) D, and astigmatism −1.14 (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or better, irrespective of pre-existing ocular disease. The overall posterior capsule opacification (PCO) rate was 20.4% and this was visually insignificant in all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy. Orbscan II elevation technology demonstrated corneal stability 2 years after uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in approximately half of the subjects 1 month postoperatively, astigmatism showed a tendency to regress towards the preoperative level with local corneal thickening at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had undergone cataract surgery. Overall, 75.3% of subjects were moderately to very satisfied with their current level of visual acuity. Conclusion: Two years after cataract surgery subjects are generally satisfied with their current level of vision and distance BSCVA is 6/12 or better in the majority of eyes. Although only a minority of eyes develop sufficient PCO to require capsulotomy 10.3% of eyes develop new vision threatening ocular pathology.

The Auckland Cataract Study: demographic, corneal topographic and ocular biometric parameters

Purpose: To determine patient demographics and the ocular biometric parameters in patients presenting for cataract surgery within the public hospital system, in a defined New Zealand population.

Microstructural assessment of rare corneal dystrophies using real‐time in vivo confocal microscopy

Purpose: To analyse and describe three cases of rare corneal dystrophy and highlight their in vivo microstructural features.

Lid-parallel conjunctival folds (LIPCOF) and dry eye: a multicentre study

Aims The study was designed to test the clinical application of the grading of lid-parallel conjunctival folds (LIPCOF) as a diagnostic test for dry eye. Methods At 12 centres in 11 countries, 272 eyes of 272 dry eye patients (75 men, 197 women) were examined. Their mean age was 52.7±16.2 years. The LIPCOF were graded according to the method of Höh et al. The tear film break-up time (BUT) was measured, and fluorescein staining and the Schirmer 1 test were performed. The subjective symptoms were evaluated by 16 questions. Results The LIPCOF score demonstrated significant positive correlations with age, dry eye disease severity and fluorescein staining (r>0.2, p<0.001), and negative correlations with BUT and results of the Schirmer 1 test (r<–0.2, p<0.001). The LIPCOF score exhibited a significant correlation with the overall subjective symptoms (r=0.250, p<0.001). The sensitivity and specificity of LIPCOF grading for discriminating between normal and dry eyes were best with the cut-off between LIPCOF degrees 1 and 2. Conclusions The displayed medium sensitivity and specificity, and good positive predictive value of the LIPCOF test support the use of LIPCOF grading as a simple, quick and non-invasive dry eye screening tool.