Ahti Tarkkanen

Epidermal growth factor is a constant component of normal human tear fluid

Epidermal growth factor (EGF) is a mitogenic polypeptide, which was first isolated from mouse submaxillary gland. Since EGF also stimulates the growth of corneal epithelial cells and only preliminary data exist on its presence in tear fluid, we studied the occurrence of human EGF (hEGF) in the tear fluid of 36 healthy persons (31 women and 5 men from 20 to 59 years of age; 60 eyes). hEGF, as measured by an immunofluorometric assay, was present in all tear fluid samples investigated. Its concentration varied from 200 to 2860 pg/ml (median, 705 pg/ml). The tear fluid hEGF concentrations differed less between the eyes of one individual than between individuals. The total amount of hEGF released to the tear fluid increased with fluid flow, but the higher the flow was, the lower the concentration of hEGF. We could not find any evidence of sex dependency in the hEGF concentrations. In demonstrating that hEGF is a normal component of human tear fluid, the results of this study suggest that hEGF may be important for conjunctival and corneal epithelial integrity.

The Merkel cell and associated neoplasms in the eyelids and periocular region

Merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles, which are probably of epithelial origin, share ultrastructural features with neuroendocrine cells, and are found in association with touch receptors. In the eyelid, they occur singly in the epidermis and external root sheaths of hairs and eyelashes, and in specialized touch spots alternating with eyelashes. Their typical electron microscopical and antigenic features include dense-core granules, intranuclear rodlets, spinous processes, and a positive reaction for specific cytokeratins, epithelial membrane antigen, neuron-specific enolase, chromogranin and synaptophysin. Merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of ten Merkel cell carcinomas occur in the eyelid and periocular region. They tend to be bulging lesions near the lid margin of elderly patients, reddish in color, and erythematous with telangiectatic vessels. The diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal Merkel cells. The tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels. One third of Merkel cell carcinomas recur, almost two thirds give rise to regional node metastases, and up to one half metastasize widely and result in death. Initial treatment should be prompt and aggressive, with wide resection and routine postoperative irradiation. Although metastatic lesions often respond to radiation therapy and cytostatic drugs, these treatments are mainly of palliative value.

Plasmin in tear fluid of patients with corneal ulcers: basis for new therapy

Abstract. In a patient with chronic corneal ulcer, resistant to conventional therapy, analysis of tear fluid revealed a high plasmin activity which could be inhibited by aprotinin, an inhibitor of serine proteinases. Therapy with topical aprotinin resulted in rapid epithelialization. After this initial patient, within a period of four months tear fluid specimens of altogether 48 patients with corneal lesions were analyzed, and 32 were found to be positive for proteolytic activity. Of these 18 were treated with topical aprotinin which rapidly promoted corneal epithelial healing. Six of these patients had been treated with conventional therapy for 3–10 weeks but proved to be completely therapy‐resistant. Our observations on three successfully treated patients with chemical burns of the cornea indicated appearance of plasmin in tear fluid after a few days correlating with cessation of epithelialization. In all patients, in which tear fluid plasmin activity was followed, the activity disappeared during aprotinin therapy correlating with corneal re‐epithelialization. In some patients with low proteolytic activity aprotinin was combined with fibronectin with a beneficial therapeutic effect. No proteolytic activity was found in the tear fluid of control individuals. These preliminary data indicate that in patients with treatment‐resistant corneal lesions inhibition of proteolytic activity can assist in epithelial healing. Such an inhibition is likely to be a prerequisite for the proteinase‐sensitive cell adhesion proteins such as fibronectin to promote epithelialization.

Evaluating cataract surgery gains by assessing patients' quality of life using the VF-7.

PURPOSE To describe the development and performance of a questionnaire designed to measure functional impairment caused by cataract. SETTING Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS The results of a visual-functioning index (VF-14) of 168 patients with first-eye cataract surgery were analyzed. Patients with significant comorbidity were excluded, leaving 142 patients for the final analysis. Snellen visual acuity measurements and complete preoperative and 4 month postoperative clinical status were performed by ophthalmologists. Outcome measures, including the VF-14, patient perception of trouble with vision, patient satisfaction with vision, and the cataract symptom score, were taken by nurses at the preoperative clinical examinations and at the 4 month postoperative visit. The Spearman rank correlation was used to determine which items of the VF-14 best correlated with a change in patient satisfaction. RESULTS Seven items of the VF-14 that best correlated with patient satisfaction were selected for inclusion in a new 7-item index (the VF-7). Based on the Spearman rank correlation, the items from best to worst were nighttime driving; reading small print; watching television; seeing steps, stairs, or curbs; reading traffic, street, or store signs; cooking; and doing fine handwork. The correlation among changes in the VF-7 score and visual acuity in the operated eye was 0.17, while the correlation among changes in the VF-7 and patient satisfaction caused by cataract surgery was high (r = .56). CONCLUSION The VF-7 was a strong predictor of change in patient satisfaction caused by cataract surgery.

Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.

AIMS/BACKGROUND: To analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. METHODS: A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The median apical and scleral tumour dose was 100 Gy (range 15-200 Gy) and 1000 Gy (range 200-1200 Gy), respectively. The median follow up time was 2.8 and 2.0 years (range 1 month to 10 years) for anterior and posterior segment complications, respectively. RESULTS: The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. The risk of radiation cataract was highest with large tumour size (T1 + T2 v T3, p = 0.0027; height < or = 5 v > 5 mm, p = 0.029; largest basal diameter (LBD) < or = 15 v > 15 mm, p < 0.0001) and location of anterior tumour margin anterior v posterior to the equator (p = 0.0003); the risk of neovascular glaucoma with large size (T1 + T2 v T3, p = 0.039; LBD < or = 15 mm v 15 mm, p = 0.021); and the risk of maculopathy and optic neuropathy with proximity of the posterior tumour margin to the fovea and the optic disc (< or = 1.5 v > 1.5 mm; p = 0.030 and p = 0.0004, respectively). In Coxs multivariate analysis the strongest risk indicator for radiation cataract (RR 1.5, 95% CI 1.4-1.6) and vitreous haemorrhage (RR 1.6, 95% CI 1.4-1.8) was the height of the tumour; for neovascular glaucoma the TNM class (RR 6.2, 95% CI 2.7-13.8); for radiation maculopathy location of posterior tumour margin within 2 mm from the fovea (RR 3.4, 95% CI 2.0-6.0); and for radiation optic neuropathy location of tumour margin within 1 DD of the optic disc (RR 6.1, 95% CI 3.0-12.4). The 3 and 5 year probabilities of avoiding enucleation were 92% and 85%, respectively. Ten eyes were enucleated--six because of recurrent tumour growth, three because of treatment complications, and one because of mistakenly suspected extraocular growth. CONCLUSION: The results suggest that the frequency of radiation related complications after ruthenium brachytherapy of uveal melanoma is acceptable, in particular as regard irradiation of small and medium sized tumours for which ruthenium therapy generally is recommended.

Iodine brachytherapy as an alternative to enucleation for large uveal melanomas.

PURPOSE To evaluate the safety and efficacy of iodine 125 plaque brachytherapy (IBT) for large uveal melanomas. DESIGN Retrospective, nonrandomized comparative trial (historical control). PARTICIPANTS One hundred twenty-one consecutive patients with a large uveal melanoma according to the Collaborative Ocular Melanoma Study (COMS) criteria who attended a national ocular oncology service. METHODS Ninety-seven patients (80%) underwent primary IBT (mean dose to tumor apex, 87 Gy) with noncollimated 20- to 25-mm plaques. Assessment of metastatic disease at death and visual outcome followed COMS guidelines. Time to low vision (20/70 or worse) and blindness (loss of 20/400 vision) in the study eye were modeled by Cox proportional hazards regression, based on both single- and repeated-failure data sets. Person-years of retained vision were calculated. MAIN OUTCOME MEASURES All-cause and melanoma-specific survival, local and distant recurrence, and preservation of vision and cosmesis. RESULTS Median tumor height was 10.7 mm (range, 4.5-16.8 mm), and largest basal tumor diameter was 16.1 mm (range, 7.3-25.0 mm). The Kaplan-Meier estimate for all-cause and melanoma-specific survival was 62% (95% confidence interval [CI], 49%-72%) and 65% (95% CI, 52%-75%) at 5 years. The corresponding estimate for local tumor recurrence was 6% (95% CI, 2%-14%) and for major cosmetic abnormality was 38% (95% CI, 26%-52%). The median visual acuity in the study eye was 20/100 at baseline and 20/1600 at 2 years after treatment. The Kaplan-Meier estimate for avoiding low vision and blindness was 11% (95% CI, 4%-24%) and 26% (95% CI, 16%-37%) at 2 years, respectively. Tumor height and location entirely posterior to the ora serrata were the most robust predictors of visual loss. In this series, 49 person-years without low vision (median, 0.6 years; range, 0.04-8.2 years) and 111 person-years without blindness (median, 1.0 years; range, 0.03-8.6 years) in the treated eye were conserved. CONCLUSIONS Iodine 125 plaque brachytherapy seems to be a safe and effective alternative to enucleation with regard to survival and local tumor control. It provides a fair chance of preserving the eye with acceptable cosmesis and a reasonable chance of conserving useful vision for 1 to 2 years.

Diagnosis and Clinical Characteristics of Ocular Lyme Borreliosis

PURPOSE To establish a diagnosis, in a group of patients we studied the characteristics of ocular Lyme borreliosis. METHODS During a two-year period, 236 patients with prolonged external ocular inflammation, uveitis, retinitis, optic neuritis, or unexplained neuro-ophthalmic symptoms were examined for Lyme borreliosis. Antibodies to Borrelia burgdorferi were measured by indirect ELISA and western blot. Cerebrospinal fluid was also analyzed by polymerase chain reaction. RESULTS Ocular Lyme borreliosis was diagnosed in ten patients on the basis of medical history, clinical findings, and serologic test results. Results of ELISA disclosed that five patients were seropositive, two patients showed borderline reactivity, and three patients were seronegative. Four of the five patients with borderline or negative results by ELISA had a positive result by western blot analysis. In one seropositive patient, polymerase chain reaction verified a gene of B. burgdorferi endoflagellin from the vitreous and cerebrospinal fluid specimen. In five of the six patients with known onset of the Borrelia infection, the ocular disorder appeared as a late manifestation. Abnormalities of the posterior segment of the eye, such as vitreitis, retinal vasculitis, neuroretinitis, choroiditis, and optic neuropathy were seen in six patients. Bilateral paralytic mydriasis, interstitial keratitis, episcleritis, and anterior uveitis were seen in one patient each. CONCLUSIONS Late-phase ocular Lyme borreliosis is probably underdiagnosed because of weak seropositivity or seronegativity in ELISA assays. Ocular borrelial manifestations show characteristics resembling those seen in syphilis.

Exfoliation syndrome in patients scheduled for cataract surgery

Abstract A series of 305 consecutive patients 30 years of age or older scheduled for cataract surgery was examined to find out the frequency of exfoliation syndrome, the predominant type of cataract, and the intraocular pressure status. The mean age of 222 (72.8%) females and 83 (27.2%) males was 71.7 (± 11.1) years (range 32 to 91 years). Exfoliation was detected in 77 (25.2%) patients. It was unilateral in 37 (48.0%) patients, the affected eye being in 29 (78.4%) cases scheduled for cataract surgery, and bilateral in 40 (52.0%) patients. Exfoliation was increased steadily with age. It was most often seen on the anterior lens capsule (88.9%). Krukenbergs spindle was seen in 31 (20.4%) eyes of patients with and in 12 (2.6%) eyes of patients without exfoliation (p < 0.001). Nuclear sclerosis predominated in eyes with (83.8%) as compared to those without (61.9%) exfoliation (p < 0.01). Posterior subcapsular cataract was less common in eyes with exfoliation (1.5%) than in eyes (21.1%) without it (p < 0.001). A tendency to slightly higher preoperative intraocular pressure was measured in eyes with exfoliation as compared to those without it, and glaucoma occurred much more frequently (33.8% vs 10.8%) in the former group (p < 0.001). Exfoliation and capsular glaucoma, which must be promptly detected to avoid surgical complications, are frequent in patients scheduled for cataract surgery.

Frequency of systemic vascular diseases in patients with primary open‐angle glaucoma and exfoliation glaucoma

Purpose:  Abnormal fibrils can be identified by electron microscopy in the heart, lung, liver, kidney, cerebral meninges and other tissues of patients with exfoliation syndrome (ES). However, a clinical association of ES with arterial hypertension (HT), ischaemic heart disease (IHD), cerebrovascular accidents and aneurysm of the abdominal aorta is debated. We conducted a national registry‐based survey to further assess the first two of these associations.

Prospective evaluation of external ocularmicrobial growth and aqueous humor contamination during cataract surgery

PURPOSE To analyze the route of aqueous humor contamination leading to the development of postoperative endophthalmitis. SETTING Department of Ophthalmology, University of Helsinki, Finland. METHODS Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsular cataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. RESULTS Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species. Staphylococcus aureus, and diptheroids. CONCLUSION The ocular surface significantly contributed to the transmission of microbes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.