What information can we give to the patient about the risks of strabismus surgery.

I hope to report the type, incidence, and clinical outcomes of severe complications from strabismus surgery in the United Kingdom and to help in the discussions involved in the consent process. The main part of the talk will revolve around a BOSU (British Ophthalmic Survey Unit) investigation. Cases were identified prospectively between 1 September 2008 and 31 August 2010. Questionnaire data were requested at the time of the complication recognition and at 6 months' follow-up. Outcome was graded I-V, with a poor or very poor outcome meaning either loss of corrected visual acuity or primary position double vision. A total of 60 completed reports of adverse events and complications were received during the study period. During the same time, ∼24 000 strabismus surgeries were carried out in the United Kingdom, yielding an overall incidence of 1 in 400 operations (95% binomial confidence, 1 per 333-500 operations). The most commonly reported complication was perforation of the globe (19 (0.08%)), followed by a suspected slipped muscle (16 (0.067%)), severe infection (14 (0.06%)), scleritis (6 (0.02%)), and lost muscle (5 (0.02%)). Overall, complications were reported in adults and children in equal numbers; however, scleritis was significantly more common in adults. A poor or very poor clinical outcome was recorded as 1 operation per 2400. The study limitations are as follows: the denominator was extrapolated from the number of surgeries in England, and there was an almost certain underreporting of cases. Complications with the potential for a poor outcome are relatively common, but the final clinical outcome is good in the majority of cases.

NAG-1/GDF15 transgenic mouse has less white adipose tissue and a reduced inflammatory response.

NAG-1/GDF15 is a TGF- ß superfamily member with poorly characterized biological activity proposed to inhibit inflammatory cytokine production. Transgenic mice expressing human NAG-1/GDF15 (NAG-1 (Tg/Lox) ) are leaner with lower body weight and are resistant to chemically or genetically induced intestinal tumors. Because of the link between obesity, inflammation, and cancer, we examined whether these mice exhibit a reduced response to inflammatory stimuli. The NAG-1 (Tg/Lox) mice had a reduced inflammatory response to LPS based on the serum levels of cytokines KC, IL-6, MCP-1, and TNF α . In contrast to literature reports and our in vivo results, NAG-1 did not inhibit LPS-induced cytokine expression in vitro in RAW264.7 cells, mouse peritoneal macrophages, or mouse liver Kupffer cells, suggesting that NAG-1/GDF15 does not directly inhibit LPS-induced inflammatory cytokine production. However, NAG-1 (Tg/Lox) mice have less white adipose tissue, the major source of inflammatory adipokines including leptin. Basal and LPS-treated serum leptin and mRNA levels in the adipose tissue of NAG-1 (Tg/Lox) mice were lower than those in WT mice. We propose that the reduced white adipose tissue and reduced leptin expression may be responsible, in part, for the reduced inflammatory response to LPS and the decrease in intestinal tumors observed in NAG-1 (Tg/Lox) mice.

Is this really a capillary haemangioma?

Periocular tumours in newborn babies are not uncommon and their diagnosis and management can be challenging. Capillary haemangioma is the most common of them and superficial ones are easy to recognise. Deep-seated (orbital) lesions can mimic various other orbital mass lesions - dermoid cysts, cellulitis, lymphangioma and the more serious rhabdomyosarcoma and neuroblastoma. A careful elicitation of history, physical examination, and appropriate orbital imaging (ultrasound for superficial ones and magnetic resonance imaging/angiography for deep-seated lesions) helps in the diagnosis. This is a brief report of a very large vascular lesion involving the lower lid with very atypical clinical features. The approach to diagnosis and successful treatment and the histological features are discussed.

Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide.

Bacterial lipopolysaccharide (LPS) is a risk factor for exacerbation of asthma and causes airway inflammation. The aim of this study was to examine the effects of disruption of prostaglandin (PG) H synthase (PGHS)-1 and PGHS-2 genes on pulmonary responses to inhaled LPS. PGHS-1(-/-), PGHS-2(-/-), and wild-type (WT) mice were exposed to 4 to 6 microg/m(3) LPS via aerosol. Enhanced pause (PenH), a measure of bronchoconstriction, was assessed using a whole-body plethysmograph before and immediately after a 4-h LPS exposure. Bronchoalveolar lavage (BAL) was performed after LPS exposure to assess inflammatory cells, cytokines/chemokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2), and PGE(2). The degree of lung inflammation was scored on hematoxylin-and-eosin-stained sections. PGHS-1 and PGHS-2 protein levels were determined by immunoblotting. All mice exhibited increased PenH and methacholine responsiveness after LPS exposure; however, these changes were much more pronounced in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). There were no significant differences in inflammation as assessed by BAL fluid (BALF) cells or lung histology between the genotypes despite reduced BALF cytokines/chemokines and PGE(2) in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). PGHS-2 was upregulated more in PGHS-1(-/-) mice compared with WT mice after LPS exposure. We conclude that: (1) airway inflammation and hyperresponsiveness are dissociated in PGHS-1(-/-) and PGHS-2(-/-) mice exposed to LPS; (2) the balance of PGHS-1 and PGHS-2 is important in regulating the functional respiratory responses to inhaled LPS; and (3) neither PGHS-1 nor PGHS-2 is important in regulating basal lung function or the inflammatory responses of the lung to inhaled LPS.

Cyclooxygenase-1 and -2 knockout mice demonstrate increased cardiac ischemia/reperfusion injury but are protected by acute preconditioning.

BACKGROUND: The purpose of this study was to examine the effects of cyclooxygenase (COX) deficiency on baseline functional characteristics and on recovery of left ventricular developed pressure (LVDP) after 20 minutes of global ischemia and 40 minutes of reperfusion in untreated and preconditioned hearts. METHODS AND RESULTS: Compared with hearts from wild-type (WT) and COX-2(-/-) mice, baseline cardiac prostaglandin (PG) E(2) and 6-keto-PGF(1alpha) levels were significantly decreased in hearts from COX-1(-/-) mice. After ischemia, cardiac PGE(2) levels increased in WT, COX-1(-/-), and COX-2(-/-) mice (P<0.05). Recovery of function (LVDP) after global ischemia in hearts from COX-1(-/-) and COX-2(-/-) mice was significantly less than in WT hearts. Pretreatment of WT mice with indomethacin for 2 days before ischemia significantly decreased LVDP recovery; however, perfusion of WT hearts with indomethacin for 40 minutes before ischemia did not significantly alter LVDP recovery. Postischemic recovery of LVDP in COX-1(-/-) and COX-2(-/-) was unchanged by perfusion with 5 micromol/L PGE(2), PGD(2), PGF(2alpha), or carboprostacyclin. Hearts from COX-2(-/-) mice showed an increase in ischemic contracture compared with hearts from WT and COX-1(-/-) mice; however, hearts did not differ in intracellular pH, ATP, or inorganic phosphate during ischemia. Ischemic preconditioning significantly improved postischemic LVDP recovery in COX-1(-/-), COX-2(-/-), and WT mice. CONCLUSIONS: Genetic disruption or 2-day chemical inhibition of COX-1 and COX-2 decreases recovery of LVDP after ischemia; however, acute perfusion with indomethacin is not detrimental. These data are consistent with protection due to the altered expression of some protein that is modulated by COX or its metabolites.

Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain.

A cDNA encoding a new cytochrome P450 was isolated from a mouse brain library. Sequence analysis reveals that this 1,958-base pair cDNA encodes a 57-58-kDa 502-amino acid polypeptide that is 70-91% identical to CYP2J subfamily P450s and is designated CYP2J9. Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450 oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system. Microsomes of CYP2J9/CYPOR-transfected cells metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid (HETE) thus CYP2J9 is enzymologically distinct from other P450s. Northern analysis reveals that CYP2J9 transcripts are present at high levels in mouse brain. Mouse brain microsomes biosynthesize 19-HETE. RNA polymerase chain reaction analysis demonstrates that CYP2J9 mRNAs are widely distributed in brain and most abundant in the cerebellum. Immunoblotting using an antibody raised against human CYP2J2 that cross-reacts with CYP2J9 detects a 56-kDa protein band that is expressed in cerebellum and other brain segments and is regulated during postnatal development. In situ hybridization of mouse brain sections with a CYP2J9-specific riboprobe and immunohistochemical staining with the anti-human CYP2J2 IgG reveals abundant CYP2J9 mRNA and protein in cerebellar Purkinje cells. Importantly, 19-HETE inhibits the activity of recombinant P/Q-type Ca(2+) channels that are known to be expressed preferentially in cerebellar Purkinje cells and are involved in triggering neurotransmitter release. Based on these data, we conclude that CYP2J9 is a developmentally regulated P450 that is abundant in brain, localized to cerebellar Purkinje cells, and active in the biosynthesis of 19-HETE, an eicosanoid that inhibits activity of P/Q-type Ca(2+) channels. We postulate that CYP2J9 arachidonic acid products play important functional roles in the brain.

The use of subtenon ropivacaine in managing strabismus with adjustable sutures.

BACKGROUND: Squint angle alterations with the use of adjustable sutures after strabismus surgery can be painful. Ropivacaine is a long-acting local anesthetic that, at low doses, produces sensory block with limited nonprogressive motor block. METHOD: We performed a double-blind, randomized, pilot study using subtenon ropivacaine or placebo at the time of surgery in patients undergoing adjustable suture surgery. Surgery was performed by the same surgeon in each case. Later in the day, the same surgeon adjusted the sutures. At the time of adjustment, the patient recorded pain using a linear pain score, and the surgeon recorded ease of adjustment using a linear score. The results of surgery were noted at 4 weeks. RESULTS: Ten patients were randomized to receive ropivacaine and 11 to receive placebo. All 10 of the ropivacaine group and 9 of the placebo group had suture adjustment. In the ropivacaine group, there was a significantly lower pain score (P <.05, Mann-Whitney U test) but no significant difference in ease of adjustment. There appeared to be no demonstrable difference in the results of surgery between the 2 groups. CONCLUSION: Ropivacaine appears to reduce the pain of postoperative suture adjustment without adversely affecting the final outcome, although it does not appear to ease the adjustment itself. This small pilot study shows promising results in postoperative analgesia in these patients, although further larger trials are recommended.

Analysis of the cytotoxic properties of linoleic acid metabolites produced by renal and hepatic P450s.

Cytochrome P450 epoxidation of linoleic acid produces biologically active metabolites which have been associated with many pathological conditions that often lead to acute renal failure. In the present study, we evaluated the ability of specific cytochrome P450s to produce linoleic acid monoepoxides. We then tested the cytotoxic properties of linoleic acid, linoleic acid monoepoxides, and corresponding diols in a rabbit renal proximal tubule model. CYP1A2, CYP2E1, CYP2J2, CYP2J3, CYP2J5, and CYP2J9 metabolized linoleic acid at rates comparable to arachidonic acid and produced linoleic acid monoepoxides as major products. Cytotoxicity studies showed that linoleic acid, linoleic acid monoepoxides, and corresponding diols are toxic at pathologically relevant concentrations (100-500 microM). Concentration-dependent studies showed that linoleic acid and linoleic acid monoepoxides are the most toxic and induce mitochondrial dysfunction prior to cell death. Cytoprotectants known to block cell death associated with mitochondrial dysfunction and oxidative stress did not prevent cell death induced by linoleic acid and linoleic acid monoepoxides. This study shows that P450s in the CYP1 and CYP2 gene families metabolize linoleic acid to linoleic acid monoepoxides and that the monoepoxides, as well as linoleic acid, disrupt mitochondrial function without causing oxidative stress.

Inherited retinal telangiectasia with glial proliferation.

We describe five patients from a family of Pakistani origin with inherited retinal telangiectasia and glial proliferation. Characteristics of this condition include: variable visual loss; peripapillary retinal telangiectasia with vascular incompetence on fluorescein angiography; glial proliferation; cystoid macular edema or altered macular pigment; retinal hemorrhage; and abnormal electroretinopathy. We discuss the similarities with and distinguishing features from other documented conditions and the mode of inheritance.

Secondary exotropia: a retrospective analysis of matched cases.

Secondary exotropia, that is exotropia following surgery for esotropia, remains frustratingly common, even among experienced strabismologists. In this study, we have compared a group of secondary exotropia cases with a matched group of cases of residual esotropia. Of the factors analyzed, only the presence of an A- or V-pattern preoperatively (P = .0077), the presence of limited postoperative adduction (P < .001), and postoperative binocular function (P = .0073) identified the secondary exotropes. The presence of reduced adduction postoperatively in subjects with secondary exotropia was a poor prognostic sign with 11 of the 13 cases requiring further surgery for poor cosmesis. The authors suggest two subclassifications of secondary exotropia.