Aqueous Flare Response Research Articles

Intraoperative and Immediate Postoperative Outcomes of Cataract Surgery using Phacoemulsification in Eyes with and without Pseudoexfoliation Syndrome.

To compare the intraoperative and immediate postoperative behavior and complications in eyes with pseudoexfoliation (PEX) syndrome with eyes having senile cataract without PEX during cataract surgery using phacoemulsification (PKE). In this prospective study, 68 eyes of 68 patients were divided into two groups: Group 1 (test) comprised 34 eyes with immature senile cataract with PEX and Group 2 (control) included 34 eyes with immature senile cataract without PEX and any coexisting ocular pathology. Phacoemulsification (modern cataract surgery) was performed on both groups through stop and chop technique and comparative analysis of the incidence of intraoperative and immediate postoperative complications was made. There was no significant difference in rates of intraoperative complications between PEX (2.9%) and Control (0%) group. The mean pupil diameter was significantly smaller in Group 1 (p<0.001). No eye in either group had phacodonesis. 58.8% of eyes in Group 1 and 29.4% in Group 2 had a harder cataract (nuclear sclerosis) ≥ grade 3 (p=0.017). PKE was performed in all eyes with cataract in both groups. Intraoperative complication (zonular dialysis (dehiscence) was encountered in only 2.9% (1 case) of eyes with PEX. PC (posterior capsule) tear (rent) with vitreous loss was seen in 2.9% eyes of Group 1 and none in Group 2. Postoperatively, IOP (intraocular pressure) and aqueous flare response were comparable between the groups. Significantly higher inflammatory cell response was observed in Group 1 (p=0.014). BCVA (best corrected visual acuity) using Snellen chart with pinhole on postoperative day1 was significantly better in the control group compared to the group with PEX (p=0.027). Phacoemulsification can be safely performed by experienced hands in cataractous eyes with PEX. The incidence of intraoperative and immediate post-operative complications in eyes with PEX was not significantly different compared to eyes without PEX in our study. Further studies among a larger population are required.

Rabbit Intraocular Reactivity to Endotoxin Measured by Slit-Lamp Biomicroscopy and Laser Flare Photometry

To evaluate the ocular reactivity of the rabbit to an intracameral injection of a dispersive ophthalmic viscosurgical device (OVD) containing various levels of bacterial endotoxin using slit-lamp biomicroscopy and laser flare photometry. Experimental, randomized, masked animal study. Thirty Dutch-Belted rabbits. The rabbits were randomized into 6 groups to receive 0.05 ml of a hydroxypropyl methylcellulose-based dispersive OVD to which had been added one of 5 different doses of bacterial endotoxin ranging from 0.02 to 1.4 endotoxin units (EUs) or a vehicle control to both eyes. The eyes were evaluated for anterior segment inflammation at baseline and 3, 6, 9, 24, 48, and 72 hours after injection using slit-lamp biomicroscopy and laser flare photometry. Corneal clarity and anterior chamber (AC) inflammation. All the corneas remained clear throughout the study. Anterior chamber cells were seen at 6, 9, and 24 hours in 60% to 100% of the eyes intracamerally injected with endotoxin-containing OVD, and the response declined rapidly after 24 hours. A dose-response effect was seen between the concentration of endotoxin and the AC cell response. The aqueous flare response in eyes injected with the 2 highest doses of endotoxin was significantly greater (P<0.05) than that of controls. The amounts of fibrin observed in the AC were random, with no apparent dose-response effect seen. The flare values as obtained by laser flare photometry were consistent with the slit-lamp biomicroscopy flare findings up to grade 3+. However, the increase in laser flare value seemed to level off in eyes with more than 3+ flare. Neither measure of flare correlated with endotoxin level. Among the parameters evaluated in this study, the AC cell response, evaluated by slit-lamp biomicroscopy and graded using a standard grading system, was found to be the most reliable indicator of the amount of endotoxin in the dispersive OVD. The use of laser flare photometry alone does not seem to be useful in detecting an ocular response to endotoxin contamination in OVDs.

Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres.

1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the maximal AFR was 28.1 +/- 2.8 (arbitrary units). 2. ECT also caused release of substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP)-27, -38 and calcitonin gene-related peptide (CGRP). The concentrations of SP and CGRP in the aqueous humour of normal, untreated eyes were 10.6 +/- 1.4 and 117.4 +/- 12.4 pmol l-1, respectively, while the concentrations of PACAP-27 and -38 were below the detection limit. After ECT the concentrations of SP, PACAP-27, -38 and CGRP were 65.0 +/- 9.6, 46.9 +/- 8.4, 50.2 +/- 5.4 and 1109.9 +/- 133.1 pmol l-1, respectively (s.e. of mean, n = 12). Conceivably, ECT evoked an antidromic activation of sensory neurones in the trigeminal ganglion with the consequent release of neuropeptides from C-fibres in the uvea and the development of neurogenic inflammation. 3. Rabbits received the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 200 mg kg 1, i.v.). This pretreatment inhibited the ECT-evoked conjunctival hyperaemia, miosis and AFR: under these circumstances the maximal reduction in pupil size was 1.9 +/- 0.1 mm while the maximal AFR was 2.7 +/- 0.9 (n = 16). L-NAME also inhibited the ECT-evoked release of SP, PACAP-27, -38 and CGRP into the aqueous humour; the concentrations of SP and CGRP were 13.2 +/- 1.5 and 204.8 +/- 33.5 pmol l-1, respectively, while PACAP-27 and -38 were below the detection limit (n = 12). 4. The ECT-evoked miosis was also inhibited by pretreatment with the tachykinin receptor antagonist D-Pal9 spantide 11 (90 nmol, intravitreal injection); under these circumstances the maximal reduction in pupil size was only 0.7 +/- 0.03 mm, indicating an important role for SP in the miotic response. Pretreatment of the eye with capsaicin, which is known to cause functional ablation of C-fibres, inhibited the conjunctival hyperaemia, miosis and AFR by 40-50%; the maximal reduction in pupil size being 2.2 +/- 0.2 mm and the maximal AFR 13.8 +/- 2.1 (arbitrary units) (n = 8). 5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters.

The contribution of nitric oxide to endotoxin-induced ocular inflammation: interaction with sensory nerve fibres.

1. The actions of nitric oxide (NO) have been investigated in an endotoxin-evoked ocular inflammatory model in the rabbit, with particular emphasis on the relationship between NO, sensory nerves (C-fibres) and the C-fibre neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP). 2. Endotoxin, injected intravitreally, evoked inflammatory responses, i.e. conjunctival hyperaemia, miosis and protein extravasation, reflected by the aqueous flare response (AFR). In control rabbits, the maximum AFR was 66.5 +/- 9.5 (arbitrary units). Pretreatment with the NO synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NAME, 200 mg kg-1) given by intravenous injection, inhibited the endotoxin-evoked responses; the AFR was 16.5 +/- 1.9 (n = 8, P < 0.001) and the conjunctival hyperaemia was abolished. 3. Endotoxin-evoked ocular inflammation is associated with the release of CGRP and PACAP from C-fibres. In the eyes challenged with endotoxin, the concentrations of PACAP-27, -38 and CGRP in the aqueous humour were 58.2 +/- 10.9, 54.4 +/- 12.4 and 5526 +/- 519 (pmoll'), respectively. L-NAME inhibited the release of PACAP-27, -38 and CGRP; the concentrations were 14.3 +/- 2.5, 13.5 +/- 2.5 and 510 +/- 67 (pmoll-1), respectively (n = 8, P < 0.01 or 0.001). 4. Intravitreal injection of 0.3 nmol CGRP induced conjunctival hyperaemia and AFR; the maximum AFR was 140.2 +/- 11.4. L-NAME suppressed the response induced by CGRP; the AFR was 23.4 +/- 5.5 (n = 8, P < 0.001). L-NAME abolished the conjunctival hyperaemia induced by PACAP-27 and -38 (0.3 nmol) and reduced the AFR. 5. The inflammatory cells that infiltrated the uvea, cornea and aqueous humour in large numbers in response to intravitreal injection of endotoxin were found to express inducible NOS. L-NAME prevented the appearance of such cells. 6. Our findings suggest that NO plays an important role in the endotoxin-evoked ocular inflammation in the rabbit: NO activates C-fibres causing release of C-fibre neuropeptides into the aqueous humour. In addition, NO mediates scme of the ocular effects of CGRP and PACAP, since L-NAME suppressed the AFR induced by these peptides.

Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye.

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.

Neuropeptide Y suppresses the neurogenic inflammatory response in the rabbit eye; mode of action.

Ocular injury in the rabbit causes miosis and breakdown of the blood aqueous barrier (aqueous flare response, AFR), reflecting a sensory nerve-mediated inflammatory response, elicited by the release of tachykinins and calcitonin gene-related peptide (CGRP) from C-fibers. Neuropeptide Y (NPY) occurs in sympathetic fibers in the eye. The study was designed to examine whether NPY and related peptides interfere with the inflammatory response to ocular injury in the rabbit in vivo. The isolated rabbit iris was studied with respect to NPY binding sites and second messenger coupling. The AFR and the miotic response to a standardized injury (infrared irradiation (IR) of the iris) were suppressed dose-dependently by NPY (0.01-1.0 nmol) injected intravitreally 30 min prior the trauma. The treated eye was compared with the contralateral eye, which received 0.9% saline and IR. The Y1 receptor agonist [Pro34]NPY, the Y2 receptor agonist NPY 13-36 and the structurally related peptide YY (1 nmol each) suppressed the AFR in response to IR. Injection of either NPY or the Y1 and Y2 receptor agonists (0.3 nmol each) suppressed the AFR evoked by exogenously applied CGRP (0.15 nmol). Saturation studies with 125I-NPY revealed both high and 'moderate' affinity binding sites in the iris. The Bmax values were 26 and 321 fmol/mg protein, respectively. NPY suppressed the forskolin-stimulated adenylate cyclase activity (IC50 value 19 nM). NPY did not affect basal or noradrenaline-induced accumulation of inositol phosphates in the iris. In conclusion, the rabbit iris seems to be rich in NPY receptors linked to inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of polyphloretin phosphate on the aqueous flare response to alpha-melanocyte stimulating hormone.

The breakdown of the blood aqueous barrier caused by topical prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) or subcutaneous alpha-melanocyte stimulating hormone (alpha-MSH) was quantified by measurements of the aqueous flare seen in the anterior chamber. Polyphloretin phosphate (PPP) administration subcutaneously was found to effectively block the protein leakage caused by all three traumatic stimuli. The same dose of PPP given intravenously inhibited effectively the flare response to PGE1 and alpha-MSH, whereas the effect of PGE2 was only slightly decreased. Significant inhibition by subconjunctival PPP was not achieved for any of the three stimuli. Assuming that PPP is a specific PG-antagonist the present results support the eariler suggestion that PGs take part in the barrier damaging action of alpha-MSH. However, it cannot be excluded that PPP acts on a step subsequent to PG. This step might be common to PGs- and alpha-MSH-effects on the barrier, explaining why PPP inhibits both types of trauma.

The effect of experimental uveitis on the uptake of prostaglandin E1 in the rabbit iris-ciliary body.

Disruption of the blood-aqueous barrier in rabbits was elicited by infrared irradiation of the iris or by alpha-melanocyte stimulating hormone (alpha-MSH) given subcutaneously. One group of animals was pretreated with topical imidazole before the injection of alpha-MSH. The aqueous flare response was followed and the rabbits were killed at the expected height of the uveitis. The uptake of 3H-prostaglandin E1 in the iris with the ciliary body was then determined and found to be significantly decreased in the rabbits in which alpha-MSH had caused a severe damage of the blood-aqueous barrier. When alpha-MSH caused a more moderate aqueous flare response the prostaglandin uptake was on the contrary significantly increased. Pretreatment of the animals with topical imidazole enhanced parallelly the prostaglandin uptake and the aqueous flare response to alpha-MSH. Topical imidazole per se was found to increase the accumulation of prostaglandin. The prostaglandin uptake values were, however, unchanged in eyes in which infrared irradiation of the iris induced a moderate flare response.

Aqueous flare response (I‐VII)

Acta OphthalmologicaVolume 55, Issue S130 p. 12-13 Aqueous flare response (I-VII) First published: April 1977 https://doi.org/10.1111/j.1755-3768.1977.tb00445.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume55, IssueS130April 1977Pages 12-13 RelatedInformation

Facilitation by imidazole of the aqueous flare response to α‐melanocyte stimulating hormone (II)

Acta OphthalmologicaVolume 55, Issue S130 p. 17-17 Facilitation by imidazole of the aqueous flare response to α-melanocyte stimulating hormone (II) First published: April 1977 https://doi.org/10.1111/j.1755-3768.1977.tb00452.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume55, IssueS130April 1977Pages 17-17 RelatedInformation

The effect of polyphloretin phosphate on the aqueous flare response to α‐melanocyte stimulating hormone (VI)

Acta OphthalmologicaVolume 55, Issue S130 p. 23-24 The effect of polyphloretin phosphate on the aqueous flare response to α-melanocyte stimulating hormone (VI) First published: April 1977 https://doi.org/10.1111/j.1755-3768.1977.tb00456.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume55, IssueS130April 1977Pages 23-24 RelatedInformation

Facilitation by imidazole of the aqueous flare response toα-melanocyte stimulating hormone

MSH, like traumata to the eye, cause a permeability disturbance in rabbits, with protein leakage into the aqueous. The MSH effect was enormously increased by instillation of imidazole or pilocarpine. The MSH effect seems to engage a different mechanism than the prostaglandin-dependent action of other agents.

Melanocyte-stimulating activity in serum and the aqueous flare response in rabbits.

Melanocyte-stimulating activity in serum and the aqueous flare response in rabbits.

Effects of the melanocyte stimulating hormone and of an induced serum factor on eye permeability and serum level of free fatty acids in the rabbit.

ABSTRACT A subcutaneous injection of melanocyte stimulating hormone (MSH) in the rabbit may give an aqueous flare response (permeability disturbance in the ciliary body) and serum from such a rabbit may induce a similar effect in another rabbit. Serum from this rabbit may in the next rabbit induce the same effect. The permeability effect obtained by serum injection is not accompanied by a free fatty acid (FFA) release, in contrast to the MSH effect. The FFA are not a prerequisite for a flare effect, though they may play a role in the production of the serum factor. The serum factor can hardly be a MSH compound.

QUANTITATIVE RELATIONS IN THE AQUEOUS FLARE RESPONSE INDUCED BY ALPHA-MELANOCYTE STIMULATING HORMONE IN THE RABBIT EYES.

ABSTRACT The aqueous flare response (AFR) to MSH is induced in an increasing percentage of animals with increasing age. The great variability of the responses and the fact that local administration of MSH is not more efficient with lower doses than by subcutaneous injection indicate that the AFR is a complex result in which general factors play a part. The analysis of the variation of the responses has led to a procedure for testing the effect of different preparations.

INCREASED PERMEABILITY OF THE BLOOD-AQUEOUS HUMOR BARRIER IN THE RABBIT'S EYE PROVOKED BY MELANOCYTE STIMULATING PEPTIDES.

The relative protein content in the aqueous humor of an intact eye can be determined by a new photoelectric method. The systemic administration of certain hypophysial polypeptides causes a transitory increase in permeability of the blood-aqueous humor barrier in the rabbit's eye. This has been denoted the “aqueous flare response” (AFR). The following peptides have been tested for their ability to cause the AFR: synthetic α-MSH, porcine α- and β-MSH, porcine corticotropin, porcine peptide I, synthetic Nα-Ac-β1–10-corticotropin and β1–10-corticotropin. The AFR provoking effect of these preparations is correlated with their melanocyte stimulating activity but not with their corticotropic activity. A number of factors influencing the response have been investigated. It is shown that an AFR is more easily evoked 1) in fasted than in normally fed rabbits, 2) in pigmented than in albino rabbits, and 3) in adult than in young animals. (Endocrinology 74: 255, 1964)