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We evaluated various technical aspects of tear collection to assess their influence on the measurement of tear histamine levels. We included several methods of collecting tears, storage of tears with and without freezing, storage for three vs ten days, and removal vs nonremoval of cells before freezing. We assayed tear samples in various groups of people with inflamed eyes. None of the various means of collecting or storing the tear samples influenced the histamine measured. The measuring technique is a stable one that requires minimal treatment of samples before assay. To date, we have found that only patients with vernal conjunctivitis have elevated tear histamine levels. Any increase of tear histamine over 10 ng/ml (geometric mean plus 2 S.D.) or any significant decrease is probably related to the disease itself and not to factors related to the technique used to measure tear histamine.

• Compound 48/80 ( N -methyl- p -methoxyphenethylamine formaldehyde condensation product) was used to selectively degranulate mast cells to induce conjunctival eosinophilia in 12 rabbits. Biopsy specimens of bulbar conjunctiva showed that eosinophils were present in all treated eyes. With repeated treatments the number of eosinophils increased; these cells were concentrated in the subepithelial and epithelial zones by day 3. Eosinophils were not found on scrapings of the bulbar conjunctiva in 75% of the rabbits that received single or multiple treatments. We conclude that deep and superficial eosinophil infiltration may be present even when eosinophils are not seen on conjunctival scrapings. Therefore, the absence of eosinophils in scrapings should not rule out the diagnosis of ocular allergy.

The perioperative management of the pupil is essential to the success of anterior segment surgery. A new dilating regimen was tested in 65 cases of cataract extraction and intraocular lens implantation. The α-adrenergic agonist, phenylephrine 2.5%, was used after pretreatment with the adrenergic (β-blocker, timolol 0.5%. This treatment successfully dilated the pupil in all but three cases, was maintained by intraoperative epinephrine infusion, and was readily reversed with intraocular acetylcholine. We conclude that this pharmacologic regimen provided a successful and easily reversible mydriasis during surgery.

• Eight widely used commercially available ocular decongestants were compared on the basis of vasoconstrictive effectiveness. The ability of these preparations to counteract histamine-induced erythema and to block its recurrence when rechallenged after one hour was evaluated in six human subjects in seven sessions. All vasoconstrictors tested were effective. No preparation was statistically different from 0.02% naphazoline hydrochloride in vasoconstrictive effect. In fact, this intermediate concentration of naphazoline (0.02%) was found to be significantly better than the other nonprescription decongestant preparations tested as a group and not significantly different from a group of higher concentrations of naphazoline.

To the Editor. —In the December 1983 issue of theArchives, Tse et al 1 reported their success in treating four patients with severe palpebral vernal conjunctivitis and one with giant papillary conjunctivitis by conjunctival incision and mucous membrane grafting. The authors claimed that by totally excising the cobblestone papillae from the tarsal conjunctiva and grafting a replacement mucous membrane, they could improve patients' symptoms and prevent corneal changes by eliminating the mechanical action of the cobblestones. Our current understanding of pathophysiologic factors and their effects on the ocular surface in vernal conjunctivitis leads us to question the importance of the mechanical relationship between giant papillae and the corneal changes in this disease. Henriquez et al 2 reported the increase in degranulated mast cell populations in the conjunctiva of patients with vernal conjunctivitis. We have shown that the level of histamine, one of the most important mast cell products, is

Histamine levels were measured in tears from normal volunteers (geometric mean, 5 ng/ml), patients with vernal conjunctivitis (16 ng/ml), and patients with a wide variety of external ocular inflammatory disease (3 ng/ml). Histamine levels were significantly higher in patients with vernal conjunctivitis than in normal subjects (P < 0.01) or patients with other types of ocular inflammation (P < 0.001). We postulate that histamine is an important mediator in the expression of the inflammatory response in vernal conjunctivitis, and that its elevation may be caused by abnormalities in the number of mast cells, the stability of the mast cells or in the system that regulates histamine.

We measured the levels of major basic protein and Charcot-Leyden crystal protein in tears from patients with ventral keratoconjunctivitis or miscellaneous inflammatory or noninflammatory ocular conditions, and from normal subjects. Patients with vernal keratoconjunctivitis had significantly increased levels of both proteins in their tears compared with the other subjects tested; levels of major basic protein seemed to correlate with the severity of the disease. The levels of Charcot-Leyden crystal protein paralleled those of major basic proteins.

• Ten normal human volunteers participated in a two-part study of H 2 -receptor activity in the ocular surface. Dimethylaminopropylisothiourea (trivial name, dimaprit dihydrochloride), a highly selective H 2 -receptor agonist, produced vasodilation without itch. Pretreatment with the H 2 -receptor antagonist, cimetidine, significantly blocked the vasodilatory effect of dimethylaminopropylisothiourea, whereas pretreatment with the H 1 -receptor antagonist, antazoline phosphate, did not. We conclude that H 2 -receptors are present in the human ocular surface.

• A case of recurrent herpes simplex virus keratouveitis was studied using both electron microscopic and viral culture techniques. We describe a patient who had a particularly violent course, including three failed grafts, endophthalmitis, and wound leak. We report the identification of virus in a quiescent failed corneal graft and retrocorneal membrane; persistence of virus enabling its culture from the vitreous; and electron microscopic identification in the cornea removed at the third transplant. The identification of cases in which viral proliferation occurs is necessary for a greater understanding of the pathogenesis of herpetic corneal disease and for determining in which particular patient steroid therapy should be avoided.

The size, weight, and plasma cell content of main and accessory lacrimal glands were examined and compared to the number of plasma cells in the conjunctiva. There were from four to 35 accessory lacrimal glands in the upper conjunctiva and a rare accessory gland in the lower conjunctiva. The total accessory gland mass was approximately one tenth of the lacrimal gland mass although the number of plasma cells was approximately 1/20 of the mass. The number of plasma-cells in the lacrimal gland was estimated to be 3,200,000; in the conjunctiva, 2,100,000; and for the accessory glands, 180,000. Because of the many plasma cells in the relatively inaccessible lacrimal gland, cells of the lymphatic series may home to the lacrimal gland by non-antigenic mechanisms.

Cellular events in the rat conjunctiva were studied at 1, 6 and 24 h following the topical application of leukotriene B4. A significant increase was noted in the number of eosinophils (p less than 0.01) and neutrophils (p less than 0.05) at 1 h and only in eosinophils at 6 h after leukotriene B4 application at the 2-micrograms dose. At the 200-ng dose, the eosinophil count was significantly elevated at 1 h only, and the number of neutrophils was not significantly changed at any time point. No significant increase in cell counts was observed at the 20-ng dose. In conclusion, certain doses of topically applied leukotriene B4 significantly increased the number of eosinophils and neutrophils in the rat conjunctiva.

Commercial preparations of two topical ophthalmic vasoconstrictors were evaluated for whitening ability, duration of action, tolerance, and rebound vasodilation in 11 normal volunteers. Both 0.02% naphazoline HCl and 0.05% tetrahydrozoline HCl significantly reduced baseline redness after a single use (Part I); however, naphazoline produced significantly more whitening than did tetrahydrozoline. Only naphazoline retained its whitening ability after ten days (Part II). The level of redness remained significantly below baseline for eight hours after a single use of either vasoconstrictor and for six hours after multiple use of naphazoline. The diminished effectiveness of tetrahydrozoline after the ten-day test period may encourage its overuse. Neither vasoconstrictor produced rebound vasodilation after discontinuation of use.

We investigated the effect of the calcium channel blocker verapamil on intraocular pressure in human volunteers. In the initial trial, 15 subjects with untreated ocular hypertension were tested. After a baseline measurement was obtained with applanation tonometry, a 40-microliter drop of verapamil, 1.25 mg/ml, was instilled in one eye. After 30 minutes, a second reading was taken. In a subsequent trial of 12 untreated ocular hypertensive subjects, the duration of action was determined using the same dose and method of delivery. Results showed that verapamil elicited a mean +/- S.E.M. change in intraocular pressure of -3.8 +/- 0.900 mm Hg in the treated eye, and -1.6 +/- 0.400 mm Hg in the untreated eye. This reduction was statistically different in both eyes (treated eye, P = .0007; untreated eye, P = .005). This decrease in intraocular pressure remained statistically significant when compared to predrug baseline values for up to ten hours.

Prostaglandin D 2 is a secondary mast cell mediator that causes redness, chemosis, mucous discharge, and eosinophil chemotaxis in the eye. It may play an important role in allergic ocular disease. Although histamine is a key mediator of allergic inflammation, antihistamine therapy provides only symptomatic relief. We added aspirin therapy to the treatment regimen of three patients with vernal conjunctivitis. Aspirin acetylates the enzyme cyclo-oxygenase, thereby preventing the formation of prostaglandin D 2 . Within two weeks after initiation of aspirin therapy, we noted dramatic improvement in conjunctival and episcleral redness and resolution of keratitis and limbal infiltration. We recommend a trial of oral aspirin as adjunctive therapy for intractable cases of vernal conjunctivitis.

We analyzed the blinking motions of ten patients with inferior punctate keratopathy and ten normal subjects by means of time-lapse motion pictures. We also determined the frequency of blinking during one-minute intervals for each individual. Four types of blinking were distinguished: complete, incomplete, twitch, and forced blink. The average blinking frequency was about the same for both groups: 16 to 17 blinks per minute. The relative proportion of complete blinks, however, was much lower in patients with inferior punctate keratopathy than in normal subjects. The impaired blinking motion may be responsible for the punctate staining of the inferior corneal epithelium by producing exposure and inadequacies in the tear film. For this reason, these patients may benefit from blink training, application of tear substitutes, or soft contact lenses more than from the customary prescription of topical cortisone eyedrops.

We compared the tear pH values of 44 normal, healthy volunteers, 20 patients with ocular disorders other than rosacea, seven patients with untreated, active ocular rosacea, and five patients with tetracycline-treated ocular rosacea. The group with untreated, active ocular rosacea had significantly more alkaline tear pH values than the other groups tested. In patients with tetracycline-treated ocular rosacea, tear pH values were not significantly different from those of normal subjects.

Tear samples from 13 normal volunteers and nine patients with vernal conjunctivitis were assayed for histamine. Tears in both groups contained histamine. The normal subjects had values ranging from 2.2 to 36 ng/ml with a mean of 10.3 ng/ml. The vernal patients had histamine values ranging from 0 to 125 ng/ml with a mean of 3,.2 ng/ml. The presence of histamine in tears indicates a role for this important mediator in both the physiologic and immunologic processes of the external eye.

A 35-year-old woman who had undergone bilateral penetrating corneal grafts for keratoconus had keratoconus in the eye that had received a graft 16 years earlier. A second penetrating keratoplasty was performed, and the excised button was examined with light and electron microscopy. Both the light and electron microscopic findings were consistent with the clinical diagnosis of keratoconus. Keratoconus in a graft for the same disease should be added to the list of late complications of successful keratoplasties.

Products of arachidonic acid metabolism, prostaglandins and leukotrienes, play an important role in ocular inflammation. In this study, we investigated the efficacies of the cyclo-oxygenase inhibitors (aspirin, indomethacin, and piroxicam) and the lipoxygenase inhibitors (N-hydroxy-arachidonamide (AH) and phenidone) in reducing ocular inflammation induced by arachidonic acid. Administering arachidonic acid topically (0.50% for rabbits and 0.25% for humans) produced a simple model for evaluating the effects of inhibitors on prostaglandins. In rabbits, aspirin, piroxicam and indomethacin all blocked lid closure and chemosis significantly. In humans, aspirin and indomethacin significantly blocked arachidonic acid-induced conjunctival injection. Neither AH nor phenidone blocked any of the signs of ocular inflammation in rabbits or humans. Further testing of phenidone in the presence of the calcium ionophore, ionomycin, also proved negative. Species specificity in arachidonic acid metabolism may account for the different results in humans and rabbits. This model may be a useful tool for comparing the relative efficacies of topical cyclo-oxygenase inhibitors in treating ocular problems.

Hyper-IgE syndrome (HIE) appears to be related to an immunoregulatory imbalance characterized by severe deficiency of suppressor T cells, elevated levels of IgE antibodies, and repeated infection of various organ systems. We report the association of HIE syndrome in two definite cases and one probable case of vernal conjunctivitis. This association suggests that T cell-mediated imbalance may be one factor in the pathogenesis of vernal conjunctivitis.

Topical application of the nonimmune selective mast-cell degranulating agent, compound 48/80, produced the signs and symptoms of ocular allergy (itching, injection, chemosis, and mucous discharge) in eight guinea pigs, eight rabbits, and nine humans. The histamine H1 receptor antagonist, antazoline phosphate, blocked itching but not vasodilation in five humans pretreated with compound 48-80. This suggests that histamine was one of the mediators released by compound 48-80-induced degranulation. Compound 48-80 may be helpful in evaluating the effects of therapeutic agents capable of modifying mast-cell degranulation and in the study of mediators involved in external ocular inflammation.

The role of the Diagnostic Methodology Subcommittee of the Dry Eye Workshop was 1) to identify tests used to screen, diagnose and monitor dry eye disease, 2) to establish criteria for test performance, and 3) to consider the utility of tests in a variety of clinical settings. The committee created a database of tests used to diagnose and monitor dry eye, each compiled by an expert in the field (rapporteur) and presented within a standard template. Development of the templates involved an iterative process between the Chairman of the subcommittee, the rapporteurs, and, at times, an additional group of expert reviewers. This process is ongoing. Each rapporteur was instructed on how to the complete a template, using a proforma template and an example of a completed template. Rapporteurs used the literature and other available sources as the basis for constructing their assigned template. The chairman of the subcommittee modifed the template to produce a standardized version and reviewed it with the rapporteur. The completed database will be searchable by an alphabetical list of test names, as well as by functional groupings, for instance, tests of aqueous dynamics, lipid functions, etc. The templates can be accessed on the website of the Tear Film and Ocular Surface Society (www.tearfilm.org). This report provides a general overview of the criteria applied in the development of tests for screening and diagnosis.

• Tarsal conjunctival scrapings of 317 patients with allergic ocular disease demonstrated that eosinophils were found infrequently in scrapings of patients with mild allergic conditions and were found in only 63% (17/27) of the patients with vernal conjunctivitis. In similar studies of a 12-year-old boy with vernal keratoconjunctivitis, no eosinophils were recovered in his scraping, even though 12 eosinophils were found in five high-power fields of his biopsy specimen. We conclude that eosinophils present in the deep and superficial conjunctival tissues may not be recovered in scrapings; their absence from scrapings should not preclude the diagnosis of allergic ocular disease.

The ability of hyaluronidase to improve akinesis in ret robu I bar anesthesia was evaluated in a doublemasked study. Forty consecutive patients undergoing cataract surgery were anesthetized with 3 ml of a 1:1 mixture of 4.0% lidocaine and 0.75% bupivacaine solution. In a predetermined randomized fashion, 2 ml of hyaluronidase (300 USP units) were added to half of the syringes, and 2 ml of saline to the remaining half. The level of akinesia was graded in six different positions of gaze. Seventy percent of the hyaluronidase group exhibited complete akinesis, while only 40% of the control group did. The mean scores for four out of six positions of gaze were significantly higher in the hyaluronidase patients than in the control group. Similarly, the hyaluronidase subjects showed a significantly higher sum score for the six sectors than did the control subjects (p=. 0001). These results show that hyaluronidase significantly enhances akinesia. It is therefore recommended that it be included in the anesthetic regimen for such surgeries.

than other lens solution preservatives, may be the most highly sensitizing of the preservatives. The lesions resembling Trantas dots in our patient represent an IgE-mediated or possibly a toxic reaction to chlorhexidine used as a preservative in the contact lens soaking solution. When contact lens wear is associated with redness and ocular irritation, hypersensitivity to chlorhexidine should be considered. Lens care for the hypersensitive patient should consist of lens storage in a sterile, unit-dose preservative free saline.

Complete records from 175 patients with 176 episodes of culture-proven bacterial keratitis treated over a 4-year period at the Massachusetts Eye and Ear Infirmary in Boston were analyzed. Sixty-three percent of the infections involved gram-positive organisms, and 40% involved gram-negative organisms; 15% were polymicrobial. There was a high incidence of infection with Staphylococcus aureus (28%), coagulase-negative staphylococci (14%), diphtheroids (14%), Pseudomonas aeruginosa (14%), and Streptococcus pneumoniae (12%). Gram stain correlation was achieved in 55%. Potential predisposing factors, usually multiple, were identified in 97% of the patients. Fifty percent of the ulcers were associated with such iatrogenic factors as prior topical corticosteroid therapy, penetrating keratoplasty, and contact lens use. Trauma occurred in only 16%. Several statistically significant associations of epidemiologic factors and outcome variables were revealed. Ninety-five percent of the ulcers resolved with therapy, but only 44% of the patients had visual acuity better than the level at admission, and 13% developed major complications.

• Tear pH was measured in 44 normal subjects by immersing the tip of a microcombination glass pH probe in the tear fluid in the inferior cul-de-sac. The normal pH range was 6.5 to 7.6; the mean value was 7.0. This method provides a rapid and accurate measure of tear pH and may better our understanding of tear physiology and tear buffering capacity.