Biomedical subjects
Publications and source records attributed to P C Donshik.
We have discussed herein the dermatologic and ocular manifestations of several inflammatory diseases. Cooperation between ophthalmologists and dermatologists can significantly enhance patient care and comfort. It is hoped that this review will stimulate increased awareness of the prevalence of ocular findings in these diseases and encourage cooperation between these specialties for the benefit of our patients.
We evaluated the efficacy of cromolyn sodium in the management of contact lens patients with GPC. Fourteen of 20 patients (70%) with moderate to severe giant papillary conjunctivitis (GPC) were able to continue wearing contact lenses with the use of 4% sodium cromolyn eye drops. These patients had all failed to stay symptom free with our standard method of treatment (i.e., discontinuing contact lens wear for 1-2 weeks; improving lens care; and refitting with different lens designs and/or polymers). This study examined the indications, therapeutic regimen, complications, and patient response to the use of sodium cromolyn in contact lens patients with GPC.
Allergic eye disease is commonly encountered in clinical practice. The external eye is exposed to a host of environmental, cosmetic, and pharmacologic antigens. Although individual responses show a wide range of variability, a number of distinctive syndromes have emerged to define the spectrum of allergic eye disease. They consist of seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and contact allergies involving the conjunctiva.
Explore the source record for details and available documents.
This study was designed to determine the presence of neutrophil chemotactic factors in the tears of patients with giant papillary conjunctivitis (BPC) secondary to contact lenses. Chemotactic activity was measured using modified Boyden chambers and the chemoattractant formylmethionyl-leucyl-phenylalanine (f-MLP) for 100 percent response. Elevated levels of chemotactic activity were found in the tears of symptomatic patients (80.8 +/- 6.4, % f-MLP) compared with control tears of asymptomatic contact lens wearers (15.7 +/- 3.3%) and non-contact lens wearers (5.6 +/- 1.2%). Using radioimmunoassay, C5a (serum-derived chemoattractant), leukotriene-B4, and interleukin-1 (immune cell-derived chemoattractants) were not detected in the tears of symptomatic patients. The authors determined whether injured conjunctival cells participate in this process by releasing neutrophil chemotactic factors. Isolated rabbit bulbar conjunctiva incubated with culture medium for 4 and 6 hr released high levels of neutrophil chemotactic factors. The release of these factors from injured conjunctiva support the premise that physical trauma of conjunctival cells induced by contact lenses may be an important component of the pathophysiology of giant papillary conjunctivitis.
We have previously reported on the release of neutrophil chemotactic factors (NCF) from injured conjunctival tissue. The present study was designed to biochemically characterize these conjunctiva-derived chemotactic factors and determine their biological activities. Bulbar conjunctiva was surgically removed from a rabbit eye and incubated with 250 microL of minimal essential medium (MEM) for 6 hours at 37 degrees C in a 5% CO2 atmosphere. Chemotactic activity was assayed using modified Boyden chambers with rabbit peritoneal neutrophils as indicator cells. Following treatment with subtilisin protease for 90 minutes, chemotactic activity of the conjunctival factors was reduced by 74%. Similarly, activity was lost after heating at 56 degrees C for 60 minutes (41% inhibition). Using ultrafiltration techniques, we showed that the majority of the chemotactic activity remained above a 100 kilodalton filter, suggesting the existence of high molecular weight factors. We also showed that the conjunctival factors are not glycoproteins and bind to both anion and cation exchange resins. When 100 microL of conjunctival supernatant was injected in the superior tarsal conjunctiva of rabbits, significant recruitment of neutrophils was evident by 4 hours. Control rabbits injected with MEM did not show neutrophil recruitment. Results of these studies indicate that NCF from traumatized conjunctival tissue are proteins (and not glycoproteins) of high molecular weight, heat labile, exhibit anionic and cationic charges, and are active in vivo.
Explore the source record for details and available documents.
A 48-year-old man has been followed for 15 months for what was clinically diagnosed as Terrien's marginal degeneration combined with anterior basement membrane dystrophy. This patient was originally referred for evaluation and consultation regarding his basement membrane changes, fluctuating vision, and recurrent erosion symptoms. This is believed to be the first reported case of Terrien's marginal degeneration associated with anterior basement membrane dystrophy.
Lactoferrin, an iron complexing protein in normal tears, is an important component of the nonspecific host defense system of the external eye. We measured tear lactoferrin levels in patients with contact lens-induced giant papillary conjunctivitis (GPC) by an enzyme-linked immunosorbent assay (ELISA). Patients with active GPC (N = 26) had significantly reduced tear levels of lactoferrin (0.876 +/- 0.42 mg/ml) compared with normal individuals (N = 12; 1.73 +/- 0.46 mg/ml, P less than 0.0003) and the control contact lens wearers' group (N = 11; 1.57 +/- 0.92 mg/ml, P less than 0.003). Patients with vernal conjunctivitis (N = 10), an ocular disease with similar histopathology, had slightly reduced concentrations of tear lactoferrin (1.22 +/- 0.59 mg/ml). Patients with inactive GPC (N = 7) had normal tear levels of lactoferrin (1.33 +/- 0.49 mg/ml). The lactoferrin to total protein ratio in the tears was significantly reduced in patients with GPC compared to normal subjects, control contact lens wearers, and patients with inactive GPC. The decreased tear levels of lactoferrin in patients with GPC may contribute to increased coating of lenses with bacteria and their products and enhanced ocular inflammation which may play a role in the pathogenesis of GPC.
Previous studies in our laboratory have demonstrated pollen-specific IgG antibodies in the tears of patients with vernal conjunctivitis (VC) and elevated tear IgG levels in patients with contact lens-induced giant papillary conjunctivitis (GPC). Tear secretions were examined for complement (C) proteins to determine the role of this effector system in the pathogenesis of these ocular disorders. The tears of VC (15) and GPC (10) patients with active disease had elevated tear levels of both C3 and factor B. By use of transferrin as a marker for the leakage of plasma proteins into the tears, most C3 was locally produced by the conjunctival tissues. Although immune complexes could not be detected in the tear secretions, increased levels of C3 des Arg were present in the tears that suggested complement activation with the generation of anaphylatoxins. These studies suggest that complement may be important in the inflammatory ocular process of VC and GPC and that the generation of anaphylatoxins (C3a), even by nonimmune mechanisms, may contribute to basophil and mast cell activation with the release of inflammatory mediators into the tear secretions.
Each of 18 patients with giant papillary conjunctivitis induced by contact lenses had symptoms of increased mucous production with blurred vision, decreased contact lens tolerance, pruritus, and giant papillae of the upper tarsal conjunctiva. When the tears were collected and analyzed for immunoglobulins, the more symptomatic eye was the left in nine patients and the right in seven patients. The fellow eyes were equally symptomatic in two patients. Tear IgE levels in patients with giant papillary conjunctivitis were significantly increased, especially in the more symptomatic eye (geometric mean, 6.9 IU/ml; P less than .01) compared with those in a control group who also wore contact lenses (2.1 IU/ml). Increased tear IgG levels (50.7 micrograms/ml; P less than .01) were found in the more symptomatic eyes of patients with giant papillary conjunctivitis. In eight of the 18 patients, tear IgM was measurable (greater than 4.7 micrograms/ml), whereas none of the control groups had detectable amounts of IgM in their tears. Studies with transferrin as a marker for the vascular leakage of serum proteins into the tears showed that local production was responsible for the increased tear immunoglobulin levels.
We studied results of 124 keratoplasties in 100 keratoconus patients; 61 men and 39 women varying in ages from 11 to 69 years with an average age of 30 years. Twenty-four patients had bilateral grafts with a 27% incidence of rejection, and 76 patients had unilateral grafts with a 13% incidence of rejection (P less than .01). Data analysis of the first year after the graft of first eyes and subsequent years after the graft of first and second eyes, however, revealed a nearly fourfold increase of rejections following second grafts, with a 17% increased chance of rejection for the first graft after the second was implanted. Only two of the bilateral and two of the unilateral grafts were irreversibly lost because of graft reaction. The major complication was the formation of posterior subcapsular cataract, which occurred in approximately 32% of the patients. The final postkeratoplasty visual acuities were significantly improved. In the patients who did not develop a cataract, 86% achieved visual acuity of 6/12 (20/40) or better. In the patients who did develop cataracts, 68% achieved visual acuity of 6/12 (20/40) or better.
Dexamethasone sodium phosphate was administered topically to one eye of rabbits with bilateral alkali corneal burns, and saline solution was administered to the contralateral eye. Topical steroids were also administered in animals with moderate corneal ulcers and were found to enhance the severity of ulceration when given during the second and third weeks following the burn. If the corticosteroids were given daily in the first six days or in the fourth and fifth weeks following the burn, they did not have an adverse effect on the cornea. Corticosteroids can be used intensively during the first week following an alkali burn, without increasing the risk of corneal melting. The mechanism for the enhancement of corneal ulceration is not a direct augmentation of collagenase activity, but probably involves the inhibition of repair processes.
Four patients with symptomatic superior limbic keratoconjunctivitis underwent resection of the superior bulbar conjunctiva. One of these patients also underwent a tarsal conjunctival resection in the other eye. Three of the patients had previously been treated by various regimens without resolution; the fourth had had no prior treatment. All four patients had immediate and continued relief of the ocular symptoms after the superior bulbar conjunctiva was excised. The patient who underwent tarsal conjunctival resection experienced only short-term relief. We studied the conjunctival tissue by light and transmission electron microscopy. Both techniques revealed abnormalities related to the bulbar conjunctival surface with keratinization of the epithelium, acanthosis, degeneration of the nuclei, and intracellular accumulation of glycogen. Inflammatory cells were minimally present. The tarsal conjunctiva appeared essentially normal.
A prominent histological feature of superior limbic keratoconjunctivitis is the presence of keratinization of the superior bulbar conjunctiva. Ultrastructurally the affected conjunctival epithelium shows all of the characteristics of keratinization as described in skin. There is a superficial layer of horny cells with reduced organelles and thickened cell membrane. In the intermediate layers, the cells contain an increased number of cytoplasmic filaments which are sometimes aggregated into dense masses, keratohyalin granules, both in the cytoplasm and in the nucleus, membrane coating granules, lysosomes and various other types of membranous structures.
Superior limbic keratoconjunctivitis (SLK) is a condition of unknown etiology. Histological signs include acanthosis, dyskeratosis, keratinization, and ballon degeneration of the bulbar conjunctival epithelium. Ultrastructural examination of biopsy material from five eyes of patients with SLK shows numerous nuclear changes in the conjunctival epithelial cells. These include abnormal distribution and aggregation of nuclear chromatin, the presence of filaments within the nucleus, and dense accumulations of cytoplasmic filaments which surround the nucleus, resulting in "strangulation" and the formation of multilobed nuclei or multinucleated cells. These changes do not appear to have been described previously in any cell type.
Explore the source record for details and available documents.
The primary objective of treatment of a thin cornea is to maintain the integrity of the anterior chamber and to control the ocular inflammation. Available methods of therapy range from simple medical means, through soft contact lenses and tarsorrhaphy, to conjunctival flaps and keratoplasty. Once perforation has occurred, if the anterior chamber has not reformed in two to three days despite patching, soft contact lenses or adhesives should be tried; if not successful, the more complicated procedures such as glued-on hard contact lens, a blow-out patch graft, or penetrating keratoplasty must be undertaken to restore the integrity of the eye.