David Lockington

Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications

Introduction The use of topical mitomycin C (MMC) has gained popularity in the management of ocular surface neoplasia. The aim of this study is to determine outcomes and complications following such treatment. Methods This study is a retrospective review of patients treated with topical MMC for ocular surface neoplasia, including primary acquired melanosis (PAM), melanoma, corneal–conjunctival intraepithelial neoplasia (CCIN), squamous cell carcinoma (SCC) and sebaceous gland carcinoma (SGC). Data regarding diagnosis, short- and long-term outcomes, and short- and long-term complications, were recorded. Results 58 patients were identified, with a mean age of 63 years and mean follow-up of 36 months. 21 received MMC as primary therapy and 37 as surgical adjuvant. The regimen was 0.04% MMC four times a day for 3 weeks on, 3 weeks off, 3 weeks on, with topical steroid and lubricants throughout. Initial clinical response was either partial or complete in 93%. Overall, 26% developed recurrent disease at a mean of 13 months post treatment. Recurrence rates by pathology were 20% PAM, 25% melanoma, 0% CCIN, 67% SCC and 57% SGC. Short-term complications occurred in 52%, but only 7% required treatment cessation. Long-term complications such as persisting keratoconjunctivitis, epiphora and corneal problems, occurred in 31%. Conclusion The results confirm the effectiveness of topical MMC chemotherapy in the management of ocular surface neoplasia. Self-limiting short-term complications were common; however, limbal stem cell deficiency appears to be a significant long-term complication of treatment, occurring in 12%.

Assessing the accuracy of intracameral antibiotic preparation for use in cataract surgery.

PURPOSE: To evaluate 2 local dilution protocols to assess the accuracy and variability of intracameral antibiotic dosage in cataract surgery. SETTING: Tennent Institute of Ophthalmology, Glasgow, United Kingdom. METHODS: Ten ophthalmic operating room nurses from 2 local hospitals participated. Oven‐dried analytical grade potassium chloride (KCl) was used as a surrogate for cefuroxime. Solutions intended for intracameral use (1.0 mg in 0.1 mL) were prepared according to the 2 protocols. Twenty samples were obtained for each protocol. Ten analytical chemists also performed both dilutions. Concentrations of KCl in each 0.1 mL sample were analyzed by flame photometry. RESULTS: Thirty samples were obtained for each protocol. The median dose after dilution was 1.17 mg (range 0.62 to 1.77 mg) for protocol 1 and 2.05 mg (range 0.52 to 7.25 mg) for protocol 2. The median was significantly higher for protocol 2 (P < .001). There was also greater variability with protocol 2. CONCLUSIONS: This study shows that the mathematical accuracy of a dilution protocol does not ensure dosage accuracy in the clinical scenario. Inadequate mixing in a 1.0 mL syringe was probably responsible for the inaccuracy of protocol 2, indicating that small‐volume syringes should not be used for mixing. However, protocol 1 had an acceptable range of variability. Replication of this study could evaluate other protocols and address concerns regarding the accuracy of intracameral antibiotic preparations. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Presence of free radicals in intracameral agents commonly used during cataract surgery

Background Free radicals are known to cause cellular damage and are present in ophthalmic preparations. Corneal defence mechanisms are bypassed in intra-ocular surgery. We evaluated commonly used intracameral agents to ascertain the presence of free radicals and investigate the possibility of anterior segment and endothelial toxicity. Methods Samples of 19 commonly used intracameral preparations were analysed for total free radical presence on an Instrument Laboratory IL600 using a Randox Kit for Total Antioxidant Status (RANDOX Laboratories Ltd, Crumlin, UK). Results Free radical concentrations for the 19 intracameral agents ranged from 0 to 3.59 mmol/l, with median value of 0.34 mmol/l (mean value 0.933±1.19 mmol/l). Phenylephrine had the highest presence of free radicals, which were considerably higher than those for 0.5% hydrogen peroxide at all tested dilutions. Other notable results included cefuroxime (0.61 mmol/l), 2% undiluted lidocaine (0.34 mmol/l) and bevacizumab (0.59 mmol/l). Conclusion The results indicate that free radicals are present in intracameral surgical agents and some are in the order of 0.5% hydrogen peroxide. The risks of endothelial damage must be considered when using multiple intracameral preparations in complicated cataract surgery. Free radicals in intracameral preparations may be a contributing cause in cases of toxic anterior segment syndrome.

Intraoperative floppy-iris syndrome: Role of the bimanual approach

Optical coherence tomography in the diagnosis of capsular block syndrome Bao et al. have reported the biochemical analysis of the entrapped liquid in capsular block syndrome (CBS). We recently had a similar case of a 67-year-old white man who had had uneventful cataract phacoemulsification with hydrophilic acrylic intraocular lens (IOL) implantation 10 years earlier. The patient presentedwith decreased vision with a significant myopic shift. At the slitlamp examination, a milky substance was found behind the IOL. We used anterior segment optical coherence tomography (OCT) to illustrate the syndrome. Figure 1 shows the bag distension with accumulation of hyperreflective fluid behind the IOL. The distance between the IOL and the posterior capsule was 2.67 mm; the anterior chamber depth was normal. Surgery consisted of irrigation and aspiration of the capsular bag. Indication for neodymium:YAG laser capsulotomy was judged to be inappropriate due to residual peripheral lens fragments. The patient recovered his initial visual acuity. Anterior segment OCT is useful in the early diagnosis of CBS.

Antioxidant properties of amniotic membrane : novel observations from a pilot study

OBJECTIVE Amniotic membrane (AM) is used to manage various debilitated ocular surface conditions. The impact of oxidative stress and free radicals on the ocular surface is increasingly being recognized. Hyaluronic acid (HA) has anti-inflammatory properties and is abundantly present in AM. In this in vitro pilot study, we investigated the potential of AM for intrinsic free radical scavenging properties. METHODS Strips of AM were incubated in sealed tubes with hydrogen peroxide (H2O2). After being sonicated, uptake of reactive oxygen species (ROS) was measured by the Amplex Red Hydrogen Peroxide/Peroxidase assay. For comparison, 1630 kDA HA was used. RESULTS There was uptake of ROS by all AM samples, which decreased with increasing concentrations of H2O2. Mean ROS uptake for 5 different AMs at 1 hour was significantly greater for 50 μM (83%; SD 11.7, SEM 5.23) compared with 100 μM (67%; SD 20.48, SEM 9.16; p = 0.028; 95% CI 2.8-29.2). The HA comparison group showed similar uptake and trend. CONCLUSION This pilot study demonstrates that AM is able to remove ROS from its environment. Demonstrating total antioxidant capacity in AM provides evidence for use as a free radical scavenger. The antioxidant properties of AM and the contribution from HA require more research.

Free radicals and the pH of topical glaucoma medications: a lifetime of ocular chemical injury?

IntroductionPreservatives in ophthalmic preparations are known to cause ocular surface damage. Excipients can also contribute to oxidative stress in the compromised ocular surface. We evaluated commonly used topical glaucoma medications to ascertain pH levels and the intrinsic presence of free radicals.MethodsSamples of 27 topical glaucoma preparations were analysed for total free radical presence using a Randox Kit for total antioxidant status. Analytical grade indicator paper was used to ascertain pH levels.ResultsFree radical concentrations for these 27 glaucoma preparations ranged from 0 to 4.54 mmol/l, with a median value of 0.66 mmol/l (mean value of 0.662 mmol/l, SD 0.839). Levels of pH ranged from 4.0 to 7.4, with a median value of 6.5 (mean 6.252, SD 0.826). There was no evidence of a direct correlation between these two variables (r=0.232, P=0.275).ConclusionThis study is the first to document the range of pH and concentrations of free radicals intrinsically present in commonly used glaucoma medications. Long-term exposure to preservatives, free radicals, and pH levels could all contribute to ocular surface damage. The effect of excipients could be responsible for patient intolerance when changing products in the compromised ocular surface.

Presence of free radicals in commonly used ophthalmic preparations

Free radicals can cause direct cellular damage, a role increasingly defined in cardiovascular disease, but less distinct in ophthalmology. Preservatives in topical medications are known to cause toxicity and cytotoxic damage to the corneal surface.1 We set out to evaluate if free radicals were present in commonly used ophthalmic preparations and if they were present in sufficient qualities to contribute to ocular surface instability. Samples of commonly used ophthalmic preparations were analysed for total free-radical presence by indirect analysis via Total Antioxidant Status (TAS kit, RANDOX Laboratories, Crumlin, UK). They were contrasted with preservative-free Minims preparations. Various solutions including 0.5% hydrogen peroxide were also assessed to provide an appropriate reference result. Fifty-six ophthalmic preparations available in outpatients were sampled, including 18 Minims preparations, seven topical …

Mathematical and computer simulation modelling of intracameral forces causing pupil block due to air bubble use in Descemet's Stripping Endothelial Keratoplasty: the mechanics of iris buckling.

Background:  Descemets Stripping Endothelial Keratoplasty has been associated with a steep learning curve. Angle closure post Descemets Stripping Endothelial Keratoplasty has been reported, either because of air posterior to the iris causing iridocorneal adhesions, or by air anterior to the iris causing pupillary block. The mechanics of floppy iris syndrome and pupil block have not been discussed.

Oral azithromycin as the systemic treatment of choice in the treatment of meibomian gland disease.

Funding sources: None. spectrum identified in GPR98, including the new ones, and made a histogram (Fig. 2b). Usher syndrome is a genetically and clinically heterogeneous autosomal recessive disorder that has an association among RP, sensorineural hearing loss and vestibular dysfunction. According to the clinical characteristics, USH can be classified into three types. For USH1, six associated genes have been identified: USH1C, CDH23, PCDH15, USH1G, CIB2 and MYO7A. Three genes have been found to cause USH2: USH2A, DFNB31 and GPR98. For USH3, only mutations in CLRN1 have been described. However, clinical and genetic heterogeneity of USH makes it a difficult task to accurately diagnose this disease at the molecular level using conventional direct sequencing. TES is an efficient and low-cost technique for sequencing hundreds of desired genes in the genome at one time. Considering there are only 10 USH genes, TES is more cost-effective thanwhole exome sequencing (WES). In this study, we demonstrated that TES can serve as a fast and efficient way to perform the diagnosis. Although there are a few reports of molecular diagnosis in Chinese USH families with truncation GRP98 mutations, our results indicate a distinctive mutation spectrum in this population. This may require further investigation with larger-sized cohorts and enrichment of the variants database. In conclusion, we identified two novel truncation mutations in GPR98 causing USH. Our results not only enhance the current knowledge of USH phenotypic and genotypic heterogeneity but also assist both genetic diagnoses and personalized treatments of the patient.

Observation of the in vivo movement of host keratocytes into donor tissue following corneal graft; a novel technique

Background/aims The cornea is a highly cellular structure that exists in a dynamic state of cell loss, renewal and replacement. The limbus contains corneal epithelial stem cells. The progenitor or stem cell of the keratocyte remains poorly defined. The authors sought to investigate the in vivo movement of corneal stromal and epithelial cells using a chromosome in situ hybridisation (CISH) technique on human tissue. Methods Four explanted sex-mismatched human corneal buttons were studied using the CISH technique to identify corneal epithelial and keratocyte cells containing the Y chromosome. Keratocyte identity and lack of infiltrating inflammatory cells were confirmed by immunohistochemistry. The sex mismatch of donor (XX) and host (XY) suggested any identified Y chromosomes cells were of host origin having migrated into the donor tissue. Results Host corneal epithelial cells were identified in all four buttons, and corneal stromal keratocytes were present in three of the four specimens in the central corneal area. Conclusion Defining the corneal cell movements and the location of the progenitor or stem cells has important clinical implications. This study has successfully used the CISH technique to demonstrate the in vivo centripetal movement of corneal stromal keratocytes and epithelial cells. The CISH technique may allow further investigation of the corneal stromal dynamics using archival tissue.