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Eicosanoids as a new class of ocular hypotensive agents. 1. The apparent therapeutic advantages of derived prostaglandins of the A and B type as compared with primary prostaglandins of the E, F and D type.

The classic primary prostaglandins (PGs), as well as some of their analogs and derivatives, are potent ocular hypotensive agents. The present studies show that A and B PGs, which are derived from PGs of the E type by dehydration and isomerization, have a much greater ocular hypotensive potency than the primary PGs of the E, F or D type. A single application of 5 micrograms of PGA2 to the cat eye in a 25-microliters volume of aqueous vehicle solution yielded a greater and more prolonged ocular hypotensive effect than as much as 100 micrograms of topically applied PGF2 alpha. As little as 1 microgram of PGA2 had a significant ocular hypotensive effect that was enhanced by three or more consecutive daily applications of the same dose. This IOP reduction, which remained significant for several days after the last of 10 daily treatments, was not associated with biomicroscopically detectable flare or invasion of the anterior chamber by cells. Although PGF2 alpha and, to a much lesser extent, PGE2 have a miotic effect in cats, PGs of the A and B type did not cause significant miosis even at doses 50- to 100-fold greater than the minimum dose required to yield significant ocular hypotension. PGA2 retained its ocular hypotensive potency when stored in an aqueous solution at room temperature for four months. The conjunctival hyperemia caused by 5 micrograms or 10 micrograms of A or B type PGs on rabbit eyes was milder and shorter in duration than that caused by the same doses of PGE2 or PGF2 alpha. These findings suggest that derived PGs, especially PGs of the A type, may have a therapeutic advantage over primary PGs for the treatment of ocular hypertension and glaucoma.

Administration, Topical↗

Latanoprost and cholinergic agonists in combination.

Latanoprost, a prodrug of a prostaglandin F(2alpha) analog, is a potent ocular hypotensive agent, reducing intraocular pressure (IOP) primarily by increasing aqueous humor drainage through the uveoscleral outflow pathway. Initial assessments in animals found that high concentrations of cholinergic agonists reduced drainage through this pathway and attenuated the effects of a PGF(2alpha) analog. This raised the question of whether latanoprost would be effective when added to the treatment regimen of patients on pilocarpine or strong miotics. In published clinical studies, latanoprost was additive to the maximally tolerated medical therapy (which included cholinergic agonists) of glaucoma patients. Multiple doses of physostigmine in healthy volunteers did not block the effect of a single drop of latanoprost during a 1-day study. One study attempting to find the optimal timing of administration of latanoprost and pilocarpine claimed to show that additivity was best when pilocarpine was given one hour after latanoprost in the evening. Two other studies found that the timing of the doses was not important. To explain the additivity of latanoprost and pilocarpine, aqueous humor dynamics were assessed in ocular hypertensive patients treated for 1 week with each drug alone and then for one week in combination. The results showed that latanoprost increased uveoscleral outflow, pilocarpine increased outflow facility, and pilocarpine did not block or attenuate the uveoscleral outflow effect of latanoprost. The result was greater IOP reduction when these drugs were used in combination than when either drug was used alone. All available evidence demonstrates that addition of latanoprost to the treatment regime of patients already taking cholinergic agonists is an effective, although not necessarily the preferred, combination of medications for the treatment of elevated IOP.

Antihypertensive Agents↗

The role of brimonidine in the treatment of open-angle glaucoma.

At present, medical therapy is the first line of attack against primary open-angle glaucoma. beta-blockers, miotics, sympathomimetics, carbonic anhydrase inhibitors, and prostaglandins have been used with varying degrees of success. The alpha 2-agonists, clonidine, apraclonidine, and now brimonidine are powerful inhibitors of aqueous humor production, thereby lowering intraocular pressure (IOP) in these patients. Brimonidine is emerging as a potential first-line therapy for primary open-angle glaucoma, with a peak IOP-lowering efficacy comparable to that of timolol, but without timolol's adverse cardiopulmonary side effects. Brimonidine promises to be an important new drug to help meet the therapeutic challenges faced by ophthalmologists in treating glaucoma.

Adrenergic alpha-Agonists↗

Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application.

Polymeric nanoparticle suspensions were prepared from Eudragit RS100R and RL100R polymer resins and loaded with flurbiprofen (FLU), with the aim at improving the availability of the drug at an intra-ocular level for the prevention of the myosis induced during extracapsular cataract surgery. Nanosuspensions were prepared by a quasi-emulsion solvent diffusion technique using different formulation parameters (drug-to-polymer ratio, initial polymer concentration, agitation speed, etc.). The resulting nanoparticles showed mean sizes around 100 nm and a fixed positive charge (zeta-potential around +40/+60 mV). Stability tests after mid-time storage (4 degrees C or room temperature) or freeze-drying were carried out to optimise a possible final pharmaceutical preparation. In vitro, dissolution tests showed a controlled release profile of FLU from the nanoparticles. In vivo anti-inflammatory efficacy was assessed in the rabbit eye after induction of an ocular trauma (paracentesis). FLU-loaded nanosuspensions did not show toxicity on ocular tissues. Moreover, an inhibition of the miotic response to the surgical trauma comparable to a control eye-drop formulation was obtained, even though an actual lower concentration of free drug in the conjunctival sac was achieved from the nanoparticle system. Drug levels in the aqueous humour were also higher after application of the nanosuspensions.

Acrylic Resins↗

Efficacy and safety profile of ketorolac 0.5% ophthalmic solution in the prevention of surgically induced miosis during cataract surgery.

This multicenter, double-masked, randomized, parallel study compared the efficacy and safety profile of ketorolac tromethamine 0.5% ophthalmic solution with that of its vehicle in the maintenance of pupillary mydriasis during cataract surgery. A total of 176 adult patients scheduled to undergo unilateral extracapsular cataract extraction and posterior-chamber intraocular lens implantation received either ketorolac tromethamine 0.5% (n = 89) or vehicle (n = 87), starting 2 hours before surgery. One drop of study medication was instilled every 30 minutes for a total of 4 drops. No epinephrine was used in the intraoperative irrigating solution. Pupil diameter was measured with a caliper at 3 time points during surgery. To ensure participant safety, biomicroscopy, ophthalmoscopy, intraocular pressure, adverse events, and preoperative and postoperative visual acuity and refractive error were also monitored. The mean change in horizontal and vertical pupil diameter from the time of the first incision to after cortical irrigation and aspiration was significantly less with active ketorolac than with vehicle (P < or = 0.014). Consequently, mean pupil diameter after cortical irrigation and aspiration was significantly greater with ketorolac than with vehicle (P < or = 0.030). No significant between-group differences were observed in the change in pupil diameter between the end of surgery and postoperative administration of a miotic agent, safety variables, or occurrence of adverse events. In this study, ketorolac tromethamine 0.5% ophthalmic solution provided effective and well-tolerated inhibition of surgically induced miosis during cataract surgery.

Aged↗

Angle closure in younger patients.

PURPOSE: Angle-closure glaucoma is rare in children and young adults; only scattered cases associated with specific clinical entities have been reported. We evaluated the findings in patients aged 40 or younger with angle closure in our database. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Our database was searched for patients aged 40 years or younger with angle closure. Data recorded included age at initial consultation, age at the time of diagnosis, gender, slit-lamp examination, gonioscopy, ultrasound biomicroscopy (from 1993 onward), clinical diagnosis, and therapy. Patients with prior incisional surgery were excluded, as were patients with anterior chamber proliferative mechanisms leading to angle closure. RESULTS: Sixty-seven patients (49 females, 18 males) met entry criteria. Mean age at the time of consultation was 34.4 +/- 9.4 (standard deviation) years (range, 3-68 years). Diagnoses included plateau iris syndrome (35 patients); iridociliary cysts (8 patients); retinopathy of prematurity (7 patients); uveitis (5 patients); isolated nanophthalmos (3 patients); relative pupillary block (2 patients); Weill-Marchesani syndrome (3 patients); and 1 patient each with Marfan syndrome, miotic-induced angle closure, persistent hyperplastic primary vitreous, and idiopathic lens subluxation. CONCLUSIONS: The etiology of angle closure in young individuals differs from the older population and is typically associated with structural/developmental ocular anomalies rather than relative pupillary block. After laser iridotomy, these eyes should be monitored for recurrent angle closure and the need for additional laser or incisional surgical intervention.

Adolescent↗

Long-term experience with timolol ophthalmic solution in patients with open-angle glaucoma.

Timolol was used by 37 glaucoma patients from 1 to 18 months. Of those 37 patients, 31 used timolol for three months or longer and 7 used timolol for over one year. Timolol produced sustained reductions in intraocular pressure with continuous administration and did not induce miosis, accommodative spasm, or other annoying side effects. Systemic absorption produced a mild slowing of resting pulse rate. In some patients, timolol's ocular hypotensive effects are additive to miotics and carbonic anhydrase inhibitors.

Adult↗

Inhibitors of surgically induced miosis.

Miosis induced by surgical trauma is a frequent problem during extracapsular cataract surgery. In experimental surgery on rabbits, the inhibitory effect on pupillary constriction of cyclo-oxygenase inhibitors, local anesthetics, capsaicin (presumed substance P depletor), sympathomimetic agents, and anticholinergic agents were studied. In eyes predilated with tropicamide, iris massage caused marked pupillary constriction. Randomized pretreatment with the following agents significantly inhibited miosis: flurbiprofen, P less than 0.005; topical anesthetics (benoxinate, P less than 0.001, cocaine, P less than 0.05, proparacaine, P less than 0.005); and retrobulbar capsaicin, P less than 0.005. No significant inhibition was shown with topical indomethacin aqueous solution (P less than 0.15), topical tetracaine (P less than 0.15), or retrobulbar lidocaine (P less than 0.15). No single agent or combination of agents blocked the total miotic response; however, a combination of flurbiprofen, benoxinate, and capsaicin blocked more than two third of the miosis. Phenylephrine, a sympathomimetic (active) mydriatic agent, was more effective than anticholinergic (passive) mydriatic agents in obtaining maximal pupillary size after surgical iris massage.

Anesthetics, Local↗

The effect of argon laser trabeculoplasty on the medical control of primary open-angle glaucoma.

Argon laser trabeculoplasty was performed in 33 eyes with primary open-angle glaucoma whose intraocular pressures were poorly controlled on medical therapy. Five eyes (three patients) were failures and underwent trabeculectomy within three months. The remaining 28 eyes were followed up for 18 months and received a complete examination at periodic intervals. Beginning three months after trabeculoplasty, an attempt was made to decrease medications in a prospective manner in order to determine the least treatment required to maintain a pressure of less than 22 mmHg. No medication could be discontinued in 39% of eyes, whereas 18% were "cured" by trabeculoplasty and required no further medical therapy for control. Nine of 14 eyes that had been treated with carbonic anhydrase inhibitors were controlled without these drugs after trabeculoplasty. In 57% of eyes, the miotic could be discontinued. A total of 82% of cases still required some medication for pressure control after laser trabeculoplasty.

Adult↗

Early loss of central visual acuity in glaucoma.

Central visual acuity is usually maintained until late in the course of glaucoma. Ten patients (5 men, 5 women) between the ages of 25 and 79 were found to have decreased visual acuity associated with central or centrocaecal scotomas early in their course. Five patients had chronic open-angle glucoma, three and pigmentary glaucoma, one and juvenile glaucoma, and one had Axenfeld's syndrome. A Marcus Gunn pupil was present in all six patients not on miotics. Most lost central acuity at pressures under 30 mmHg. Seven patients had vision of 20/200 or less. All with marked visual loss had a cup disc rate of .8 or greater. Other causes were carefully ruled out. Proposed mechanisms for the development of these central defects include either double Bjerrum scotomas which extend centrally or early papillomacular bundle involvement due to temporal cupping. This study demonstrates that decreased vision with associated central field loss can be a relatively early finding in glaucoma.

Adult↗

After the eyes are straightened what is the ophthalmologist's responsibility?

Occlusion, glasses, prism therapy, miotics, fusional vergence stimulation, plus more surgery are required frequently in various combinations for a high percentage of patients whose strabismic eyes are straightened by surgery. Amblyopia is a serious sequelae befalling children who are dismissed following satisfactory surgery. Their best possible postoperative status is monofixation (absence of bifixation), despite having straight eyes. Unless they alternate fixation, amblyopia is prone to either occur or recur. Also, either a gradual change in motor innervation to the extraocular muscles or a cicatricial scarring process may subtly cause subsequent strabismus. Hence, despite straight eyes postoperatively the surgeon's responsibility continues.

Amblyopia↗

Angle-closure glaucoma complicating ciliochoroidal detachment.

Acute angle-closure glaucoma complicating ciliochoroidal detachment developed in eight eyes of six patients. The clinical presentation was uniform: extremely shallow central anterior chamber depth, flat peripheral anterior chamber, closed angle, and elevated intraocular pressure (IOP). There were three patients with uveal effusion syndrome, two with posterior scleritis, and one with an arteriovenous malformation. Cycloplegia, along with aqueous suppressants and corticosteroids, successfully resolved the acute glaucoma in all eyes. This rare, secondary glaucoma must be differentiated from primary angle-closure glaucoma, because the treatment is markedly different. Although primary angle-closure glaucoma is treated with miotics and peripheral iridectomy, such therapy may worsen the glaucoma in eyes with angle-closure glaucoma due to a ciliochoridal detachment.

Aged↗

Malignant glaucoma after laser iridotomy.

Malignant glaucoma was initially reported as developing after surgery for glaucoma. Subsequently, associations with trauma, inflammation, and the use of miotic agents, as well as spontaneous occurrence have been noted. Laser iridotomy has been assumed to avoid the risk of subsequent malignant glaucoma in eyes with angle-closure glaucoma by avoiding surgical incision of the eye. However, the authors report six cases of malignant glaucoma after laser iridotomy. In all but two cases, medical therapy for the malignant glaucoma resulted in deepening of the anterior chamber and normalization of the intraocular pressure. Malignant glaucoma recurred in five of the patients, and two patients had malignant glaucoma in the fellow eye.

Adult↗

Long-term outcome of initial ciliary ablation with contact diode laser transscleral cyclophotocoagulation for severe glaucoma. The Diode Laser Ciliary Ablation Study Group.

PURPOSE: To learn the long-term outcome of ciliary ablation with diode laser contact transscleral cyclophotocoagulation (TSCPC) in eyes with recalcitrant, severe glaucoma. METHODS: Twenty-seven eyes of 27 patients with medically and surgically uncontrollable glaucoma and no previous ciliary ablation enrolled in this study. After baseline measurements and informed consent, the authors performed contact TSCPC. There were 14 pseudophakic, 7 aphakic, and 6 phakic eyes; 15 of these had primary open angle glaucoma and the remainder had various secondary or open- or closed-angle glaucomas. Median follow-up was 19 months (range, 6 weeks to 27 months). Initially after laser surgery, glaucoma medications were continued, except for a 2-week interruption of miotics; the ophthalmologist later adjusted medications in accordance with the patient's status. The authors define failure of TSCPC in two ways, based on IOP measurements during two consecutive study examinations 6 weeks or more after intervention or at the final examination: (1) less than 20% intraocular pressure (IOP) reduction from baseline, and (2) either less than 20% reduction of IOP from baseline or IOP greater than 22 mmHg. RESULTS: For 27 eyes, the baseline IOP (mean +/- standard deviation) was 36.4 +/- 12.4 mmHg (range, 20-70 mmHg). The mean IOP at last examination was 20.3 +/- 8.7 mmHg. With failure definition 1, the cumulative probability of success was 84% at 1 year and 62% at 2 years. With failure definition 2 the cumulative probability of success was 72% at 1 year and 52% at 2 years. At the last examination, 19 eyes (70%) had visual acuity improved within one line of visual acuity at eligibility. One of these eyes, with light perception vision at entry, declined to no light perception. Three eyes (11%) lost two lines of vision and five (19%) lost three or more lines. CONCLUSIONS: Contact diode laser TSCPC yields long-term improvement of IOP and preservation of visual acuity in a substantial proportion of eyes with severe, medically uncontrolled glaucoma.

Adult↗

Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination.

OBJECTIVE: This study aimed to analyze the denervation and reinnervation history of individual segments of the iris sphincter in patients with Adie's syndrome. DESIGN: The irises of these patients were retroilluminated by shining an infrared-rich light through the lower eyelid and sclera and viewing the transilluminated iris from the front with an infrared-sensitive video camera. The irises of the same group of patients also were videotaped through a slit-lamp camera using routine frontal illumination. Both of these techniques also were used to examine a series of normal subjects. PARTICIPANTS: A total of 61 patients with Adie's syndrome or Adie's-like denervation of the iris sphincter (from surgery, trauma, or radiation) and 10 normal subjects were studied. MAIN OUTCOME MEASURES: Slit-lamp examination results of the segmental movement of the iris were compared to the infrared transillumination pattern of the iris sphincter before and during the light reflex, before and during the near-vision reaction, before and during eye movement, and before and after the application of dilute pilocarpine and 1% pilocarpine. RESULTS: Whenever an iris sphincter segment contracted, it also became denser by using these techniques. Reinnervated iris segments failed to contract to light but did contract and became denser with a near effort or with eye movement. Segments supersensitive to pilocarpine became denser than adjacent segments without supersensitivity, but atrophic-appearing segments looked translucent and thin, failing to become denser, even with 1% pilocarpine. CONCLUSIONS: The innervational history and current status of each clock-hour segment of the iris sphincter can be determined using this technique of videographic infrared transillumination, and the progression and pattern of iris denervation and reinnervation can be determined in patients with Adie's pupil. A miotic Adie's pupil that is "tonic," even in darkness, was found to be associated with a dense pattern of infrared transillumination in sphincter segments, which the authors interpret as being associated with a rich reinnervation from accommodative fibers. Segments that become densely reinnervated appear to lose their cholinergic supersensitivity.

Adie Syndrome↗

[Argon laser iridoplasty in the treatment of angle closure glaucoma with plateau iris syndrome].

INTRODUCTION: Plateau iris predisposes to the onset of an angle-closure glaucoma attack without pupillary block. This is a morphological anomaly of the iris characterized by anterior insertion, root thickness greater than the norm, and anterior rotation of the ciliary processes into the posterior chamber, pushing the base of the iris into the angle. Argon laser iridoplasty is useful to retract the peripheral iris using the thermal effect of the laser to widen the iridocorneal angle. MATERIALS AND METHODS: The study investigated nine eyes of five patients who had had iridoplasty for iris plateau angle-closure glaucoma, diagnosed by dynamic gonioscopy (or indentation gonioscopy) and confirmed by ultrasound biomicroscopy (UBM). There were four females and one male, with a mean age of 42.2 years (range, 30-53 years). The mean intraocular pressure (IOP) before iridoplasty was 21.1 mmHg. The number of antiglaucoma treatments was 1 or 2, with all patients receiving miotic treatment. All patients had undergone argon laser iridotomy beforehand to remove the pupillary block frequently associated with iris plateau. Iridoplasty was done in two sessions with postoperative IOP-lowering treatment. The laser parameters used were: duration, 0.3 s; power, 500 mW; diameter, 300 microm. RESULTS: The postoperative IOP evaluated at 1 month was 14.4 mmHg with a reduction in the hypotensive treatment. No treatment was prescribed for four eyes, a single hypotensive treatment for four eyes, and two hypotensive medications for one eye. DISCUSSION: Pure iris plateau syndrome, leading to closure of the angle, is very rare compared to pupillary block, but these two mechanisms often co-exist. The physiopathology explains that the mechanism of isolated iris plateau is not modified by iridectomy. However, the advantage of argon laser iridoplasty, which retracts the periphery of the iris so as to widen the iridocorneal angle, must be emphasized. This technique can alleviate the need for high-risk filtering surgery, but longer follow-up is necessary to evaluate its duration and efficacy.

Adult↗

Effects of Solanum melongena (garden egg) on some visual functions of visually active Igbos of Nigeria.

Solanum melongena LINN (garden egg) or bitter tomato is an economic flowering plant belonging to the family Solanaceae and widely distributed throughout the temperate and tropical regions. Members are mostly herbaceous plants, and the fruit is berry and the seeds have large endosperm and are grown mainly for food and medicinal purposes. The effects of bolus consumption of 10 g of S. melongena were undertaken on visually active male volunteers so as to determine its ocular complications. Results showed that the pupil size was reduced (23%), NPC was decreased (9%) and the AA was increased (22%) and the intraocular pressure dropped by 25% while there was no effect on VA, and the habitual phoria. The miotic effect lowered the intraocular pressure appreciably and the reduced NPC which was still within normal range did not produce any vision discomfort. The increased AA and convergence excess positively correlated provide an efficient visual mechanism. It is suggested that S. melongena would be of benefit to patients suffering from raised intraocular pressure (glaucoma) and convergence insufficiency.

Administration, Oral↗

Ocular dynamics of systemic aqueous extracts of Xylopia aethiopica (African guinea pepper) seeds on visually active volunteers.

Xylopia aethiopica, African guinea pepper, is an angiosperm belonging to the family Annonecae, and used mainly as spice and in traditional medicine. The ocular dynamics of bolus consumption of 300 mg total dose was undertaken on visually active volunteers with a view to finding its ocular effects or complications. Results showed that the aqueous extract of X. aethiopica was neither a miotic nor a mydriatic, but lowered the intraocular pressure (17.48%), reduced the near point of convergence (31.1%) and increased the amplitude of accommodation (8.98%) which are positively correlated (r=0.95). On the other hand, the systemic extract had no effect on the visual acuity at far and near as well as the phoria status at the appropriate distances. The convergence excess resulted in esophoria and the increased amplitude of accommodation placed greater demand on accommodation mechanism without any discomfort. The nonspecific mechanism of action makes it a safer spice which can be exploited in the management of exophoria and raised intraocular pressure (glaucoma) in instances where the efficacy of the older conventional drugs is insufficient.

Adult↗