Bronchiolitis obliterans as a long-term sequela of Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are characterized by widespread skin and mucosal blistering and necrosis. The triggers and long-term sequelae in children may differ from those reported for adults. Bronchiolitis obliterans (BO) is an uncommon complication, with only 15 previously reported cases, but can lead to significant long-term morbidity, requiring lung transplantation in some cases. We report three children with nondrug-related SJS (n = 1) and TEN (n = 2) who developed BO. Two were treated with intravenous immunoglobulin therapy (2-2.4 g/kg) and all three survived. We highlight salient learning points from our cases and potential pitfalls in diagnosis of BO, including delayed onset, and we also review the literature.

Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial.

BACKGROUND: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis. OBJECTIVES: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis. METHODS: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics. RESULTS: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported. CONCLUSIONS: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.

Expression of haematopoietic stem cell markers, CD133 and CD34 on human corneal keratocytes.

AIM: To study the expression of CD133 and CD34 antigens on cultured human keratocytes over time. METHODS: Primary cultures of human corneal stromal cells were established from explants derived from cadaver eye donors. The cultures were sorted for CD133+ and CD34+ cells using magnetic beads. Both the primary cultures and secondary passages of sorted cells were further analysed by flow cytometry and western blot analysis for expression of the same antigens over time. RESULTS: Four different cell populations-namely, CD133+, CD133-, CD34+ and CD34-, were identified in the culture samples. Two further specific subgroups were identified by flow cytometry: CD133+/CD34- cells and CD133+/CD34+ cells. Expression of CD133 declines more than CD34 with time in cell cultures. Although most cells lost expression of these markers, small populations retained staining up to 5 weeks in culture. CONCLUSION: Human keratocytes express the haematopoietic stem cell markers CD133 and CD34. This expression decreases with time in culture, with most but not all cells losing expression. On the basis of these markers, the corneal stroma shows a heterogeneous population of cells. Expression or down regulation of expression of these molecules could represent different stages of activation of these cells.

The management of retinal vein occlusion: is interventional ophthalmology the way forward?

Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Despite its frequency treatments for RVO are unsatisfactory and include several that have not been tested by large, well designed, prospective, randomised controlled trials. There is also the lack of long term follow up in many of the available small uncontrolled studies, and the timings of interventions are haphazard. This review aims to evaluate the current knowledge relating to the pathogenesis, suggested treatments for the different types of RVO, and their complications. Isovolaemic haemodilution is of limited benefit and should be avoided in patients with concurrent cardiovascular, renal, or pulmonary morbidity. Evidence to date does not support any therapeutic benefit from radial optic neurotomy, optic nerve decompression, or arteriovenous crossing sheathotomy on its own. Vitrectomy combined with intravenous thrombolysis may offer promise for central RVO. Similarly, vitrectomy combined with arteriovenous sheathotomy intravenous tissue plasminogen activator may offer benefits for branch RVO. RVOs occur at significantly high frequency to allow future prospective randomised controlled studies to be conducted to evaluate the role of different therapeutic modalities singly or in combination.

Pattern recognition receptors in microbial keratitis.

Microbial keratitis is a significant cause of global visual impairment and blindness. Corneal infection can be caused by a wide variety of pathogens, each of which exhibits a range of mechanisms by which the immune system is activated. The complexity of the immune response to corneal infection is only now beginning to be elucidated. Crucial to the cornea's defences are the pattern-recognition receptors: Toll-like and Nod-like receptors and the subsequent activation of inflammatory pathways. These inflammatory pathways include the inflammasome and can lead to significant tissue destruction and corneal damage, with the potential for resultant blindness. Understanding the immune mechanisms behind this tissue destruction may enable improved identification of therapeutic targets to aid development of more specific therapies for reducing corneal damage in infectious keratitis. This review summarises current knowledge of pattern-recognition receptors and their downstream pathways in response to the major keratitis-causing organisms and alludes to potential therapeutic approaches that could alleviate corneal blindness.

Fine needle diathermy occlusion of corneal vessels.

PURPOSE: To develop a novel technique, fine needle diathermy (FND), for the occlusion of corneal vessels and to evaluate its safety and efficacy in a series of patients. METHODS: Fourteen patients were treated with FND to occlude corneal vessels. Patients were categorized into four groups: group 1 (n = 4), high risk patients with stromal vascularization before keratoplasty; group 2 (n = 2), patients with progressive lipid keratopathy; group 3 (n = 4), post keratoplasty patients with active rejection episodes associated with vessels; and group 4 (n = 4), patients with disciform vascularized scars with recurrent inflammation. The success of the treatment in terms of vessel occlusion and the clinical outcome were monitored. RESULTS: All patients in group 1 had successful corneal transplantation, and the grafts remained clear without graft rejection. Patients in group 2 with lipid keratopathy had 100% obliteration of vessels with stabilization of corneal scar. All four patients in group 3 had complete regression of vessels with reversal of graft rejection. Patients with vascularized disciform scar had resolution of the inflammation without recurrence. Average follow-up was 10.3 months (minimum, 6 months; maximum, 24 months). No serious complications were observed with FND. CONCLUSIONS: FND is a useful and inexpensive technique that can serve as an adjunct or alternative to laser occlusion for the treatment of established corneal vessels. It is fairly safe and effective, although complications such as intrastromal bleeding and crystalline deposits can occur and at times it may have to be repeated once or twice to achieve the desired result.

In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics.

PURPOSE: To image peripheral blood leukocyte traffic in the normal retinal and choroidal vasculature and to quantify the differences in the circulation dynamics between normal and concanavalin A (ConA)-activated leukocytes. METHODS: Normal or ConA-activated splenocytes were fluorescently labeled in vitro with 6-carboxyfluorescein diacetate (CFDA) and reinfused in vivo where they were tracked in the retinal and choroidal circulations of syngeneic rats by means of a scanning laser ophthalmoscope (SLO). Simultaneous digital and video images were captured for as long as 30 minutes, and the initial 15 seconds of image sequences and leukocyte dynamics were analyzed from digitized images by recording the velocity of trafficking cells and the number of stationary cells that accumulated with time, using a customized software package. RESULTS: Mean velocity (+/-SD) was 29.8 +/- 15.3 mm/sec in the retinal arteries, 14.7 +/- 7.2 mm/sec in the retinal veins, and 3.0 +/- 3.6 mm/sec in the retinal capillaries. Mean velocity in the choroidal vessels was 6.1 +/- 6.0 mm/sec. No significant difference in leukocyte velocity was found between activated and normal leukocytes in any of the vessel systems. However, activated leukocytes were observed to accumulate more within the choroidal vasculature (P < 0.001) and the retinal capillaries (P < 0.001) than in control animals, but not in larger retinal vessels. CONCLUSIONS: A technique to measure the kinetics of circulating leukocytes in vivo has been developed. Although leukocyte activation itself is insufficient to cause slowing of leukocyte velocity, the data indicate that leukocyte adherence to endothelium can be induced in the absence of local or systemic activating stimuli.

Structure-function studies of S-antigen: use of proteases to reveal a dominant uveitogenic site.

Retinal S-antigen induced experimental autoimmune uveitis (EAU) is a severe, predominantly T-cell mediated inflammatory disease of the uveal tract and retina of the eye. Pretreatment of LEW rats with the monoclonal antibody, MAbS2.4.C5, which defines an epitope in S-antigen, has been shown to effectively inhibit the subsequent induction of EAU with S-antigen. Using synthetic peptides and cyanogen bromide fragments of S-antigen we found the binding site of MAbS2.4.C5 to be located at the carboxy terminus of the molecule corresponding to amino acid positions 375 to 380. Limited Staphylococcus aureus V8 protease digestion yielded several polypeptide fragments including one large 43 kD fragment which retained antibody binding to a variety of both polyclonal and monoclonal antibodies which identify epitopes that span the length of the S-antigen. This treatment, however, completely destroys the MAbS2.4.C5 binding site and dramatically reduces uveitopathogenicity. Limited trypsin and papain digestion, on the other hand, had little effect on pathogenicity or on MAbS2.4.C5 binding to S-antigen or its peptide fragments. These results indicate that the carboxy-terminus of S-antigen plays a predominant role in the pathogenesis of EAU.

Presoaking with BSS used for thin manually dissected DSEK (TMDSEK): a viable option for thin DSEK.

AIM: To describe a novel technique for the safe manual dissection of thin donor lenticules in 10 consecutive patients undergoing DSEK surgery. METHODS: A key element of our new technique was to presoak the donor cornea in balanced salt solution (BSS) for 30 min before manual dissection. The cornea was placed on an artificial anterior chamber and pressure in the chamber was maintained at 80 mm Hg. The limbus of the donor cornea was incised to the same depth as the central corneal thickness. Lamellar dissection was started with the short side of the Morlet dissector (Duckworth & Kent Ltd) and completed using the lamellar (less sharp) end of the Morlet dissector. Outcomes of 10 consecutive cases of thin manually dissected DSEK (TMDSEK) were prospectively analysed for thickness and visual outcome. RESULTS: Mean graft thicknesses measured less than 100 µm at 1 month post surgery (mean thickness 90.7 µm, range 48-137 µm, SD 29.96 µm). Presoaked donor corneal pachymetry was strongly negatively correlated with graft thickness (correlation r=-0.75, P<0.05). DISCUSSION: Our dissection technique achieves consistently thin endothelial donor corneal grafts that can be safely produced with minimal financial investment and no limitations on surgical time. This technique is likely to be of significant importance for a large proportion of the eye centres where microkeratomes may not be routinely available.

Long-term outcomes of Fine Needle Diathermy for established corneal neovascularisation.

BACKGROUND/AIMS: Corneal neovascularisation (CoNV) can lead to significant ocular comorbidity with reduction in vision and cosmesis. A number of techniques have been described to reduce CoNV, but these can be expensive. Our study aimed to determine the safety, efficacy and long-term outcomes of fine needle diathermy (FND) for CoNV. METHODS: A 5-year retrospective study identified all cases of FND. Indications, intraoperative complications, and postoperative visual acuity, after treatment and retreatments, were documented, along with the procedure time. Evidence of regression and number of retreatments were identified. RESULTS: 56 eyes from 52 patients underwent FND for CoNV. The main indications included herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated with extent of CoNV (p=0.044). One complication was noted during the procedure-an intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42) showed regression with two or less treatments. Mean post-FND acuity was 0.72 (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months). CONCLUSIONS: In the largest case series reported, FND appears to be a safe and effective technique in the long term to induce regression of CoNV, with significant improvement in the VA of patients with HSK.

The journey to femtosecond laser-assisted cataract surgery: new beginnings or a false dawn?

Femtosecond laser-assisted cataract surgery (FLACS) represents a potential paradigm shift in cataract surgery, but it is not without controversy. Advocates of the technology herald FLACS as a revolution that promises superior outcomes and an improved safety profile for patients. Conversely, detractors point to the large financial costs involved and claim that similar results are achievable with conventional small-incision phacoemulsification. This review provides a balanced and comprehensive account of the development of FLACS since its inception. It explains the physiology and mechanics underlying the technology, and critically reviews the outcomes and implications of initial studies. The benefits and limitations of using femtosecond laser accuracy to create corneal incisions, anterior capsulotomy, and lens fragmentation are explored, with reference to the main platforms, which currently offer FLACS. Economic considerations are discussed, in addition to the practicalities associated with the implementation of FLACS in a healthcare setting. The influence on surgical training and skills is considered and possible future applications of the technology introduced. While in its infancy, FLACS sets out the exciting possibility of a new level of precision in cataract surgery. However, further work in the form of large scale, phase 3 randomised controlled trials are required to demonstrate whether its theoretical benefits are significant in practice and worthy of the necessary huge financial investment and system overhaul. Whether it gains widespread acceptance is likely to be influenced by a complex interplay of scientific and socio-economic factors in years to come.

Increased conjunctival expression of protease activated receptor 2 (PAR-2) in seasonal allergic conjunctivitis: a role for abnormal conjunctival epithelial permeability in disease pathogenesis?

AIMS: Aeroallergen exposure to the conjunctival epithelium in seasonal allergic conjunctivitis (SAC) may induce a cellular stress response that disrupts the barrier properties of the conjunctival epithelium, resulting in allergic disease. Whether such changes occur in SAC is unknown. Epithelial permeability is known to be increased when protease activated receptor 2 (PAR-2) is activated. We evaluated the expression of PAR-2 in patients with SAC-in-season (SACS) and compared it with control non-atopic subjects or those with out-of-season allergic conjunctivitis (OSAC). METHODS: Six SACS, eight normal and four OSAC specimens were examined immunohistochemically for PAR-2 and quantified in a masked fashion for the percentage of epithelia stained for each marker using Image-J software. Conjunctival epithelial heights were measured in all groups to confirm the presence of allergic eye disease. RESULTS: Mean percentage staining of PAR-2 was significantly greater in SACS that in normal specimens (73.4 ± 15.4% vs 32.8 ± 30.0%, p=0.038) or in OSAC (73.4 ± 15.4% vs 1.4 ± 2.2%, p=0.01). Mean conjunctival epithelial height was significantly raised in SACS (63.8 ± 9.0 µm) versus controls (44.7 ± 11.2 µm) (p=0.003, unpaired t test). CONCLUSIONS: Conjunctival epithelial PAR-2 is significantly upregulated in SAC. This supports the view that disruption of the barrier properties of the conjunctival epithelium is an important event in SAC pathogenesis.