An in vitro assessment of the thermoreversible PLGA-PEG-PLGA copolymer: Implications for Descemet's membrane endothelial keratoplasty.

BACKGROUND: To explore the use of a thermoreversible copolymer gel coating to prevent donor tissue scrolling in Descemet's membrane endothelial keratoplasty (DMEK). METHODS: PLGA-PEG-PLGA triblock copolymer was synthesised via ring opening polymerisation. Two formulations were fabricated and gelation properties characterised using rheological analyses. Endothelial cytotoxicity of the copolymer was assessed using a Trypan Blue exclusion assay. Thickness of the copolymer gel coating on the endothelial surface was analysed using anterior segment optical coherence tomography (OCT) (RTVue-100, Optovue Inc.). Gold nanoparticles were added to the copolymer to aid visualisation using OCT. Prevention of Descemet membrane donor scrolling was represented via a novel, in vitro, immersion of copolymer coated donor graft material. RESULTS: Two different formulations of PLGA-PEG-PLGA copolymer were successfully fabricated and the desired peak gelling temperature of 24°C was achieved by polymer blending. Application of 20%, 30% and 40% (wt/vol) polymer concentrations resulted in a statistically significant increase in polymer thickness on the endothelium (p < 0.001). There was no detectable endothelial cytotoxicity. The polymer was easy to apply to the endothelium and prevented scrolling of the DMEK graft. CONCLUSION: This PLGA-PEG-PLGA thermoreversible copolymer gel could be exploited as a therapeutic aid for preventing DMEK graft scrolling.

Visual evoked potential (VEP) and multifocal electroretinogram (mfERG) in ocular syphilitic posterior segment inflammation.

The aim of this study is to correlate multifocal electroretinogram (mfERG) and visual evoked potential (VEP) changes with visual acuity and clinical features in patients with posterior segment inflammation secondary to syphilis. A retrospective interventional case series of 4 patients with visual loss secondary to syphilitic uveitis is reported. The mfERG (P1) showed diminished amplitudes and prolonged latency in 7 affected eyes. Visual acuity rapidly improved 2 weeks after initiation of therapy. OCT demonstrated anatomical recovery at 1 month. In three patients, visual acuity was restored to 6/6 at 6-9 months but mfERG responses remained significantly reduced and delayed for 12-15 months before recovery to normal levels. One patient developed a retinal detachment, but achieved 6/9 vision at 30 months. VEP changes, interpreted in combination with mfERG responses, showed evidence of optic nerve involvement in 6 eyes. Ocular findings, including posterior placoid chorioretinitis, are important diagnostic features of secondary and tertiary syphilis. Visual acuity and clinical recovery occur early with appropriate diagnosis and treatment, and precede full electrophysiological recovery of the outer retina-RPE complex. Ophthalmologists have the opportunity to play a key role in undetected or missed diagnoses of syphilis, and with appropriate treatment the visual prognosis is excellent.

Severe conjunctivochalasis in association with classic type Ehlers-Danlos syndrome.

BACKGROUND: Inferior conjunctivochalasis is common, but is rarely severe enough to require conjunctival excision. This report describes a patient with severe conjunctivochalasis who was subsequently diagnosed with Ehlers Danlos Syndrome, Classic Type. CASE PRESENTATION: A patient suffering from foreign body sensation, frequent blinking and bilateral inferior conjunctivochalasis was referred and treated by topical ocular lubrication. However, no improvement was observed prompting potential excision of conjunctivochalasis. Following patient consultation and clinical diagnosis including hypermobile joints and skin elasticity, poor wound healing and wide scar morphology, Ehlers-Danlos syndrome was confirmed in the patient. CONCLUSION: This case highlights the need for direct patient questioning and provides the first reported association between conjunctiovochalasis and Ehlers-Danlos syndrome.

Surgical management of aphakia.

Despite the safety and efficacy of cataract surgery, intraoperative complications can hamper the ability to place an intraocular lens in the capsular bag. With vast numbers of cataract surgeries performed daily, complications occur often enough that every ophthalmologist should be equipped with techniques to manage aphakia. Medical management of aphakia used to be commonplace but these techniques have their disadvantages including thick bulky lenses, poor cosmesis, and aniseikonia. Surgical management of aphakia overcomes these disadvantages and offers patients the possibility of a spectacle and contact lens-free lifestyle. This article reviews the various options of surgical management of aphakia and their advantages and disadvantages. Comparison of outcomes between techniques and a protocol for deciding between techniques is presented.

A modified transconjunctival technique for botulinum toxin chemodenervation of levator palpebrae superioris for corneal protection.

BACKGROUND: Botulinum toxin (BTX) is useful for inducing temporary ptosis in patients with ocular surface disease. However, transcutaneous BTX often causes inadvertent superior rectus (SR) paresis. Furthermore, Muller's muscle is unaffected by transcutaneous BTX, resulting in lagophthalmos and incomplete ptosis. METHODS: We report a novel BTX injection technique, in which the upper lid is double everted over a Desmarres retractor, and BTX injected transconjunctivally at the superior aspect of Muller's muscle, where it lies close to levator palpebrae superioris. RESULTS: In our series of 21 patients, one had inadvertent subcutaneous BTX and developed incomplete ptosis. The remaining 20 patients had complete ptosis within 48 h. No patients had SR underaction. CONCLUSION: We conclude that transconjunctival BTX injection is safe, effective, and superior to transcutaneous BTX injection, because of the low risk of superior rectus underaction and incomplete ptosis.

Influence of stereopsis on the ability to perform simulated microsurgery.

PURPOSE: To determine whether impaired or absent stereopsis affects the ability to perform simulated microsurgical tasks. SETTING: University of Edinburgh, United Kingdom. DESIGN: Prospective randomized cross-over study. METHODS: Visual acuity and stereoacuity were measured. A band-pass filter was placed over the nondominant eye to reduce stereoacuity to 150 seconds of an arc (partial stereopsis), or the nondominant eye was completely occluded (absent stereopsis). Participants completed a computerized surgical simulator task 3 times with a randomized testing order (normal stereopsis, absent stereopsis, and partial stereopsis). The task involved using forceps to grasp and position objects in the anterior chamber. Outcomes included area of ocular injury, time to task completion, and overall score. RESULTS: Ocular damage area was significantly worse with partial stereopsis (P = .002) and worse still when stereopsis was absent (P < .001 for normal vs absent stereopsis and P = .005 for partial vs absent stereopsis). The median ocular damage area was 3.55 mm (interquartile range [IQR], 1.21-5.88 mm) with normal stereopsis, increasing to 6.10 mm (IQR, 3.96-12.47 mm) with stereopsis reduced to 150 seconds of an arc and to 9.25 mm (IQR, 4.93-18.70 mm) with no stereopsis. Time taken to complete the task increased and overall score decreased as stereopsis was reduced. The overall score decreased from 53% (IQR, 22.5-82%) under normal stereopsis to 0% (IQR, 0-43.5%) with absent stereopsis. CONCLUSIONS: Impaired stereopsis was associated with worse microsurgical performance, which may have implications for surgical training. The absence of stereopsis resulted in worse performance than partial reduction in stereopsis.

Rapidly progressive idiopathic lenticular astigmatism.

A myopic 43-year-old woman with early nuclear sclerotic cataract developed more than 11.0 diopters (D) of astigmatism over a 6-month period. This was found to be lenticular in origin. Phacoemulsification with intraocular lens implantation was performed, resulting in residual astigmatism of 0.75 D. To our knowledge, this is the first case of rapidly progressive lenticular astigmatism in an otherwise healthy eye with early nuclear sclerotic cataract.

Perineural infiltrates in Pseudomonas keratitis.

We describe 2 cases of contact lens-related microbial keratitis caused by infection with Pseudomonas aeruginosa in which perineural infiltrates were observed at presentation. In both cases, examination by confocal microscopy was negative for Acanthamoeba cysts but bacterial cultures and microscopy of corneal scrapings were positive for P aeruginosa. Both cases responded rapidly to treatment with topical levofloxacin with no significant long-term sequelae. These observations indicate that perineural infiltrates may occur in Pseudomonas keratitis without underlying Acanthamoeba infection and are, therefore, not pathognomonic of Acanthamoeba infection.

Management of intraoperative iris prolapse: stepwise practical approach.

Iris prolapse is not an uncommon occurrence during cataract surgery. It usually occurs through the main incision during hydrodissection and is commonly associated with floppy-iris syndrome; however, it can manifest in cases with no known predisposition and can occur at any stage during surgery. The mechanism is explained by the Bernoulli principle and its effect on iris position during the movement of fluid within the eye. Predisposing factors are iris configuration, anterior chamber depth, and position and architecture of the corneal tunnel. Strategies for prevention and management include the use of pharmacological agents, ophthalmic viscosurgical devices, and iris retractors. These strategies can be augmented by alteration and adaptation of the surgeon's technique.

Tissue transglutaminase (TG-2) modified amniotic membrane: a novel scaffold for biomedical applications.

The amniotic membrane (AM) is considered as a natural cell culture substrate and has occasionally been exploited in regenerative medicine especially for ocular surface reconstruction and dermal wound healing applications. However, its use is limited by its relatively weak mechanical strength, difficulty during manual handling and susceptibility to proteolytic degradation in vivo. Therefore, in this study we aimed to enhance the mechanical and biological characteristics of the AM by enzymatically cross-linking it using tissue transglutaminase (TG)-a calcium-dependent enzyme capable of forming stable ε(γ-glutamyl)lysine cross-linkages. Using a biological catalyst such as TG does not only prevent denaturation during sample preparation but also minimizes the potential of residual chemical cross-linking agents compared to alternative methodologies. Human AM, sourced from elective caesarean sectioning, were treated with TG, bovine serum albumin and/or a no-treatment control. Samples were then compared in terms of their physical and (scanning electron microscopy (SEM), transparency, mechanical strength, susceptibility to proteolytic degradation) biological characteristics (in vitro cell culture, activation of dendritic cells (DC)) and their in vivo biocompatibility/angiogenic capacity (chick chorioallantoic membrane assay). TG-treated AM exhibited enhanced mechanical strength and greater resistance to proteolytic/collagenase degradation compared to the control(s). SEM imaging of the TG-treated membrane summarized a significantly closer association and greater interconnectivity of individual collagen fibres yet it had no effect on the overall transparency of the AM. In vitro cell culture demonstrated no detrimental effect of TG-treatment on the AM in terms of cell attachment, spreading, proliferation and differentiation. Moreover, an 'immune response' was not elicited based on extended in vitro culture with human-monocyte-derived DC. Interestingly, the TG-treated AM still allowed angiogenesis to occur and in some instances, demonstrated an enhancement compared to the control (n = 5). We hereby demonstrate that treating the AM with the cross-linking enzyme, TG, results in a novel biomaterial with enhanced mechanical and biological characteristics. Above all, this modified membrane demonstrates greater strength, maintains in vitro cell growth, retains optical transparency and allows angiogenesis to occur without inducing an immune response. Altogether, this study demonstrates the feasibility of TG as an alternate cross-linking treatment for the production of novel biomaterials and suggests that TG-treated AM may now be more commonly exploited as a therapeutic dressing for ocular or wound applications.

Eyelid avulsion repair with bi-canalicular silicone stenting without medial canthal tendon reconstruction.

AIMS: To evaluate the functional and cosmetic success rate of combined canalicular laceration and eyelid avulsion repairs using the bi-canalicular Crawford stent, without the concomitant placement of a medial traction suture to repair medial canthal tendon (posterior limb) avulsion. METHODS: Retrospective, non-comparative consecutive case series of 40 consecutive patients with traumatic eyelid avulsion injuries associated with canalicular laceration from 1997 to 2003 who underwent surgical repair using the bi-canalicular Crawford stent were included. All patients underwent surgical repair of the canalicular laceration under general anaesthesia using the bi-canalicular stent. Meticulous anastomosis of the torn canaliculus was undertaken. No attempt was made to suture the avulsed medial canthal tendon (posterior limb) to the periosteum of the posterior lacrimal crest. RESULTS: Blunt trauma was the most common mechanism of injury and the inferior canaliculus was most commonly involved. Of the 37 patients who attended postoperative follow-up, 24 patients had no subjective symptoms of epiphora. Minimal, mild and moderate epiphora was present in seven, five and one patient respectively. Thirty-three patients had excellent cosmetic repositioning of the lid; two developed medial ectropia and a further two patients had lid margin notching but good lid position. Eight patients had premature stent loss. CONCLUSIONS: Bi-canalicular stenting achieved excellent cosmetic results in eyelid avulsion injuries, by facilitating adequate tissue realignment without the need for a posterior lacrimal crest fixation suture. Good functional results were achieved and were comparable with previous studies.

Hormone therapy and intraocular pressure in nonglaucomatous eyes.

OBJECTIVE: The influence of sex hormones on intraocular pressure (IOP) has been the focus of recent debate. Previous studies investigating the effects of hormone therapy (HT) on IOP in postmenopausal women have produced conflicting results but have been limited by small numbers of participants. The aim of our study was to compare IOP in women without glaucoma taking HT with those not taking HT. METHODS: A prospective cross-sectional study of postmenopausal women visiting a single ophthalmic medical practitioner was conducted. All women with a history of intraocular disease, a family history of glaucoma, or refractive error exceeding +/-5 diopters were excluded. Applanation tonometry was used to measure IOP, and participants were then asked if they were current HT users. RESULTS: A total of 263 participants were recruited, of whom 91 reported current use of HT; 172 had never used HT. Within the HT group, 33 were taking an estrogen-therapy and 58 were taking a estrogen-progesterone therapy. Mean IOP in the HT group was significantly lower than that in the non-HT group; the mean difference was 1.41 mm Hg (P < 0.001). This difference remained statistically significant after statistical correction for age, use of systemic beta-blockers, and time of IOP measurement. There was no significant difference in mean IOP between women taking combined versus those taking estrogen-only preparations. CONCLUSIONS: Our study showed that IOP was significantly lower in women taking HT than in those who had never taken HT, even after removing other possible influences on IOP. The IOP-lowering effect of HT deserves further investigation to explore whether it may represent a possible new therapeutic modality for glaucoma.

The visualisation of vitreous using surface modified poly(lactic-co-glycolic acid) microparticles.

AIMS To demonstrate the potential use of in vitro poly(lactic-co-glycolic acid) (PLGA) microparticles in comparison with triamcinolone suspension to aid visualisation of vitreous during anterior and posterior vitrectomy. METHODS PLGA microparticles (diameter 10-60 microm) were fabricated using single and/or double emulsion technique(s) and used untreated or following the surface adsorption of a protein (transglutaminase). Particle size, shape, morphology and surface topography were assessed using scanning electron microscopy (SEM) and compared with a standard triamcinolone suspension. The efficacy of these microparticles to enhance visualisation of vitreous against the triamcinolone suspension was assessed using an in vitro set-up exploiting porcine vitreous. RESULTS Unmodified PLGA microparticles failed to adequately adhere to porcine vitreous and were readily washed out by irrigation. In contrast, modified transglutaminase-coated PLGA microparticles demonstrated a significant improvement in adhesiveness and were comparable to a triamcinolone suspension in their ability to enhance the visualisation of vitreous. This adhesive behaviour also demonstrated selectivity by not binding to the corneal endothelium. CONCLUSION The use of transglutaminase-modified biodegradable PLGA microparticles represents a novel method of visualising vitreous and aiding vitrectomy. This method may provide a distinct alternative for the visualisation of vitreous whilst eliminating the pharmacological effects of triamcinolone acetonide suspension.

Management of intraoperative floppy-iris syndrome-associated iris prolapse using a single iris retractor.

Tamsulosin is an alpha(1)-adrenergic antagonist known to be linked with intraoperative floppy-iris syndrome (IFIS), which is characterized by iris atonicity and a propensity toward progressive intraoperative pupil constriction and iris prolapse. We present 2 strategies for managing IFIS-associated iris prolapse. Placement of a single subincisional iris retractor following reposition of the prolapsed iris was the more successful approach. We recommend consideration of this approach in all cases of iris prolapse.

Silicone oil-induced corneal perforation following complex retinal detachment.

PURPOSE: To report a case of silicone oil-induced corneal perforation following complex retinal detachment surgery. METHODS: Case report. RESULTS: Two months following a second retinal detachment repair, the patient presented to eye casualty with a corneal perforation secondary to silicone oil keratopathy. CONCLUSION: The pathophysiology of silicone oil-related perforation is not clearly understood. Poor corneal nutrition due to the presence of oil may be an important contributory factor. Close monitoring of patients for early signs of silicone oil keratopathy could preempt perforation.

Limbal epithelial crypt: a model for corneal epithelial maintenance and novel limbal regional variations.

OBJECTIVE: To determine the distribution of cell membrane proteins and extracellular matrix proteins around the limbal epithelial crypt (LEC) compared with adjacent limbus and corneal epithelium. METHODS: Serial histological sections of human corneoscleral limbus rims were stained with antibodies of interest by standard immunohistochemistry. RESULTS: Superficial cells of the limbus were desmoglein 3 positive, compared with the negative basal cells of the limbus that correspond to cells with more stemlike properties. The LEC had a much lower proportion of desmoglein 3 staining in comparison. Tenascin C staining demonstrated regional variations of the limbus depending on their association with the LEC. Limbus that was associated with or adjacent to the LEC had a greater tenascin C expression compared with normal limbus, whereas the LEC demonstrated the greatest tenascin C expression. CONCLUSIONS: Based on these and similar results previously reported for connexin 43, we propose a novel model on the mechanism of corneal surface epithelium maintenance involving 3 different limbal regions: zone 1, limbus including the LEC; zone 2, limbus associated with the LEC; and zone 3, limbus distant to the LEC. CLINICAL RELEVANCE: The noted limbal variations may influence the selection of the donor site for limbal grafts in the future.