Drug survival of biologic therapies for palmoplantar pustulosis: A nationwide study.

BACKGROUND: Biological therapies have established efficacy in psoriasis vulgaris. However, palmoplantar pustulosis (PPP) has proven difficult to treat, and data on drug survival in these patients remain scarce. OBJECTIVE: To investigate drug survival of biological treatments in a nationwide cohort of patients with PPP. METHODS: We included all patients treated for PPP with a biologic from a prospective Danish nationwide registry between 2007 and 2019. Descriptive statistics were reported. Drug survival was calculated for all patients and specified for the most frequently used biologics. Drug survival was reported as median time to discontinuation. Kaplan-Meier plots were used to visualize drug survival. Trajectories of Dermatology Life Quality Index (DLQI) scores were plotted by interpolating between the different visits with a dermatologist for each treatment course. RESULTS: We identified 85 individual patients who received biological therapy for PPP across 194 treatment courses during follow-up. Of the included treatment courses, 151 (77.8%) were discontinued. The most frequent cause of discontinuation was ineffective response to treatment (54.3%), while 18.5% of courses were discontinued due to adverse events. The median drug survival across all therapies for PPP was 9.3 (Inter quartile range (IQR), 3.9-25.6) months. Ustekinumab demonstrated the longest median time to discontinuation of 14.6 (IQR, 9.1-51.8) months. The proportion of bio-naive patients in treatment at 12 months were according to drug 47.9% for adalimumab, 64.3% for ustekinumab and 40.0% for secukinumab. For bio-experienced, it was 58.2% adalimumab, 54.5% for ustekinumab and 51.4% for secukinumab. CONCLUSIONS: The treatment of PPP poses significant challenges, with limited drug survival observed across all therapies regardless of prior experience with biologics. Ustekinumab demonstrated the longest median drug survival. Notably, patients discontinuing therapy due to inefficacy exhibited higher DLQI scores, highlighting the importance of personalized treatment selection and timely consideration of therapy changes when inefficacy is established.

Corneal grafting for keratoconus in mentally retarded patients.

PURPOSE: To compare the results of penetrating and non-penetrating corneal grafting procedures in mentally retarded keratoconus patients. METHODS: In the years 1974-2000 41 mentally retarded patients with keratoconus (33 with Down syndrome) were operated with corneal grafting. Mean age at operation was 36.7+/-10.8 years. Three different surgical procedures were used (no randomization): penetrating keratoplasty (n=16), lamellar keratoplasty (n=5) and epikeratophakia (n=20). In a retrospective study, the non-penetrating procedures (lamellar keratoplasty and epikeratophakia) were compared to the penetrating keratoplasties with regard to graft survival and frequency of serious complications. Mean follow-up time of all grafting procedures was 80+/-58 months. RESULTS: All cases of serious complications (irreversible rejection, wound leakage or perforation) occurred in the penetrating keratoplasty group (p=0.0005). Older age at operation (p=0.011) adversely influenced the frequency of serious complications. Overall five-year survival was 74.9%. Graft survival was not related to surgical procedure, but rather to age at operation (poorer survival in older age, p=0.012) and degree of retardation (poorer survival in patients with more severe retardation, p=0.051). CONCLUSIONS: Because of the safety and low frequency of complications, epikeratophakia is recommended as the grafting procedure of choice in the majority of mentally retarded with keratoconus. In selected cases (good cooperation, age < or =40 years, and a good peripheral corneal thickness) penetrating keratoplasty may be performed, which, if uncomplicated, often will give better functional/optical results.

[Orbital tumors]. / Svulster i orbita.

BACKGROUND: Orbital tumours are relatively uncommon, and few series of patients with such tumours have been reported from Scandinavia. Here we present the experience of a Norwegian referral centre. MATERIAL AND METHODS: We have retrospectively evaluated the records of 278 patients with orbital tumours hospitalized at the Department of Ophthalmology, Haukeland University Hospital from 1961 to 1999. RESULTS: In 177 patients, a benign tumour was present, while 96 patients suffered from malignant disease. In five cases, the malignant potential of the tumour could not be assessed. A total of 71 different histological entities were observed. Surgical treatment performed at our department was in 22 patients exenteration, in 87 lateral orbitotomy, in 47 anterior orbitotomy and in 41 biopsy through an anterior approach. INTERPRETATION: This series illustrates the wide panorama of space-occupying lesions that may be present in the orbit. Since the lesions are rare and management in many cases complex, the treatment should be centralized to an eye department with a defined interest in orbital disease.

Light microscopy of uveoscleral drainage routes after gelatine injections into the suprachoroidal space.

PURPOSE: To visualize the suprachoroidal space and to study the morphology of possible uveoscleral drainage routes in the human eye. METHODS: Indian ink stained gelatine was injected directly into the suprachoroidal space of 7 human donor eyes. Those quadrants where gelatine appeared in the episcleral venous network were cut in their entirety in consecutive sections and examined by light microscopy. RESULTS: Gelatine was observed in the connective tissue surrounding scleral vessels and nerves. Gelatine was also traceable in fine, endothelium-lined channels at the inner aspect of the anterior sclera. These channels seemed to originate at the inner surface of the sclera, close behind the scleral spur, and communicate with the intrascleral venous plexus. CONCLUSION: Fluid is drained from the suprachoroidal space through the perivascular and perineural spaces of scleral blood vessels and nerves. In addition, this study indicates that there are preformed channels at the inner aspect of the anterior sclera, capable of draining fluid directly into scleral veins.

A new hereditary conjunctivo-corneal dystrophy associated with dermal keloid formation. Report of a family.

PURPOSE: To report a previously undescribed hereditary conjunctivo-corneal dystrophic disease associated with keloid formation in a woman and her two sons. METHODS: We have been able to follow the affected members of the family with clinical examinations over many years. In addition, they have been examined with chromosome analyses and X-ray examination of their hands. RESULTS: The mother and the oldest son have both shown a very similar clinical development, with fibrovacular tissue gradually covering the cornea, leading to severe visual loss in both eyes. In the youngest boy, the condition started at a later age, and to date only one eye is affected. All three patients have developed keloid scars on their hands. CONCLUSION: The described condition seems to represent a previously unreported, autosomal dominant inherited disease. A congenital defect in the cell differentiation of the limbus region is discussed as a possible pathogenesis.

Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the pig eye.

Eyes from pigs were studied by corrosion casting technique. Batson's mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the suprachoroidal space. Following polymerisation of the injected mixture the surrounding tissue was dissolved with 10% natrium hydroxide. Macroscopic and scanning electron microscopic findings in casts of the suprachoroidal space are presented. The outer (scleral) surface of the casts was rough, with a fish-scale-like appearance caused by fine lamellas between the sclera and choroid, running from the inner layers of the sclera traversing the space anteriorly to the choroid. Frequently, irregular, Y-shaped branches deriving from the outer surface of the casts were observed. They corresponded to the perivascular space of the vortex veins and represent a possible uveoscleral drainage route for aqueous humour.

Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the human eye.

Human cadaver eyes were studied by corrosion casting technique. Batson's mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the suprachoroidal space. Following polymerisation of the injected mixture the surrounding tissue was dissolved with 10% natrium hydroxide. Macroscopic and scanning electron microscopic findings in casts of the suprachoroidal space are presented. Due to transscleral drainage of resin from the suprachoroidal space, different types of branches deriving from the outer (scleral) surface of the casts were found. Some of these branches corresponded to the perivascular spaces of both ciliary vessels and vortex veins. In addition, we found branches probably representing channels deriving directly from the suprachoroidal space, communicating with the intrascleral venous plexus. Such channel systems have previously not been described, and their possible relation to the uveoscleral drainage of aqueous humour is discussed.

Quantification of the endotoxin-neutralizing capacity of serum and plasma.

A new procedure for quantifying the endotoxin-neutralizing capacity (ENC) of plasma or serum is described. Serially diluted samples were preincubated with endotoxin (lipopolysaccharide; LPS) and the sample dilution producing 50% inhibition of Tachypleus amebocyte lysate activation was measured by a Limulus peptide C enzyme-linked immunosorbent assay. The assay was not subject to interference from plasma or serum at a 500-fold dilution. The ENC of fresh sera from 120 healthy human donors, determined with Salmonella abortus LPS, had a median value of 7.7 kEU/ml (95% confidence limits 3-24 kEU/ml). Values for heparinized fresh plasma were close to those for the corresponding sera. Serum ENC varied greatly with different types of LPS. Neutralization of LPS by serum was rapid, heat-labile, and fully reversed by acidification. Addition of 2 mM EDTA to the serum diluent or pretreatment of LPS with 0.5% deoxycholate enhanced the ENC of serum about 25-fold or 10-fold respectively. The neutralization of LPS by polymyxin B or lysozyme could be demonstrated by the ENC assay, while that by human serum albumin, fibronectin or anti-LPS immunoglobulins was only detected in the presence of 2 mM EDTA. The kinetic changes of LPS and ENC during rabbit endotoxemia were also determined. The ENC assay may be used to study the significance of plasma ENC in Gram-negative infections and to identify the components contributing to plasma ENC.

Refractive state and correction of refractive errors among mentally retarded adults in a central institution.

In a population of 212 mentally retarded, retinoscopy could be performed in 342 eyes in 182 patients. Of these, 334 eyes were phakic. Hypermetropia of +5 or more was encountered in 20 eyes (6.0%), while 26 (7.8%) had a myopia of -5 or more. The most striking finding was a high number of severe astigmatism, cylindrical power of -3.25 or more being present in 29 eyes (8.7%). Glasses were initially prescribed to 88 patients. Six months after the prescription, 59.1% used their glasses regularly. Aspects of glass prescription to mentally retarded are discussed in the paper.

Do we operate too many cataracts? The referred cataract patients' own appraisal of their need for surgery.

A questionnaire was sent to 379 patients referred for cataract extraction, asking them to assess their visual disability and their need for surgery. Two hundred and seventy-nine patients (73.6%) answered the questionnaire, this group being representative for the 379 patients regarding all relevant variables. The patient's answers were analyzed in relation to data extracted from their referral notes (visual acuity, monocular pseudophakia, age, sex, place of residence, referring ophthalmologist). The overall level of self-reported visual problems and need for cataract surgery were significantly correlated to a reduced best-eye visual acuity, although the correlation factor was low. A similar correlation between the subjective need for surgery and a worst-eye visual acuity < or = 6/24 was also found. Forty-seven patients (16.9%) answered that cataract surgery was not needed for the time being, and this attitude was not significantly correlated to the visual acuity, provided the acuity was > or = 6/24 in the best eye and > or = 6/36 in the worst eye. One hundred and twenty patients (43.0%) felt that their visual disability was so severe that they had to be operated within 1 month and 67 patients (24.0%) within 3 months, while 45 patients (16.1%) felt that surgery could be postponed for at least 6 months. Age, sex, place of residence and the presence of monocular pseudophakia were not found to significantly influence the level of self-reported visual problems. Only 18.3% preferred to be treated as out-patients.

Retrobulbar anesthesia with and without hyaluronidase in extracapsular cataract surgery. A prospective, randomized, double-blind study.

Eighty patients with senile cataract were subjected to a planned extracapsular cataract extraction (ECCE) with implantation of a posterior chamber intraocular lens. Retrobulbar anesthesia was administered by injection of 4 mg lidocaine 2% with adrenalin. In 40 patients 150 I.U. hyaluronidase (Kinetin) was added to the anesthesia. The hyaluronidase group had a significantly lower frequency of iris prolapse, and deeper anterior chamber, both before and after expression of the lens nucleus. Possible mechanisms explaining the beneficial effect of hyaluronidase in extracapsular cataract surgery are discussed.

Epikeratophakia for keratoconus in mentally retarded patients. The use of fresh, free-hand made lamellar grafts.

Epikeratophakia for keratoconus was done in 11 mentally retarded patients, using fresh, free-hand made lamellar grafts. The mean follow-up period was 31.5 months. The grafts remained clear and well adapted in 7 cases (63.6%). Necrosis of the lower part of the graft occurred in 3 eyes (27.3%), and was probably caused by persisting epithelial defects. Only one of these grafts had to be removed. Despite concurrent eye diseases, such as cataract and possible amblyopia, an improved overall visual function was reported in 5 of the 11 patients (45.5%). No vision-threatening complications related to the epikeratophakia surgery was found.

Epikeratophakia for keratoconus. Long-term results using fresh, free-hand made lamellar grafts.

Epikeratophakia using fresh, free-hand made corneal grafts was done in 16 patients with keratoconus. The follow-up period averaged 27.8 months (range 13-45 months). A significant improvement of visual acuity was obtained (p = 0.002), and 14 of the 16 eyes (87.5%) achieved a corrected visual acuity greater than or equal to 6/12. The spherical equivalent and the cylindrical refractive error were reduced (p less than 0.05), and a significant flattening of the central corneal curvature was obtained (p less than 0.002). The mean postoperative central corneal astigmatism was 4.25 D. Postoperatively, the mean central corneal thickness was 0.670 mm, and the mean central thickness of the epithelialized graft was 0.336 mm. Six patients reported some postoperative glare or blurring of vision, despite a visual acuity greater than or equal to 6/9 on the Snellen chart. No significant subjective or objective changes were noticed after the 6-month postoperative follow-up visit.

Multiple-dose, dose-response relationship for the topical carbonic anhydrase inhibitor MK-927.

The multiple-dose, dose-response curve of MK-927 was studied in a five-center, double-masked, randomized, placebo-controlled, parallel study of 2%, 1%, and 0.5% MK-927 in 76 patients with bilateral primary open angle glaucoma or ocular hypertension and intraocular pressure greater than 24 mm Hg following washout of ocular hypotensive medications. Patients received doses at 8 AM and 8 PM for 14 days, and parallel 12-hour intraocular pressure curves were performed prestudy and on day 14, with 4-hour curves on days 1 and 4. There was a significant dose-response relationship, with 0.5% MK-927 twice daily being a minimal-effect dose. Both 1% and 2% MK-927 were active through 12 hours postdose, and peak mean percent decrease in pressure at 2 hours postdose was 18.6% and 20.6%, respectively.

Keratoprosthesis. I. Results obtained after implantation of 12 one-piece prostheses. A retrospective, follow-up study.

A total of 12 one-piece keratoprostheses were implanted in 6 eyes of 6 different patients with bilateral blinding, severe corneal disease with no possibility for a successful corneal transplantation. The prosthesis and the surgical procedure used are described. The short-term results were good, with 4 of the 6 patients obtaining a substantial visual improvement. In the remaining 2 patients preexisting pathology in the posterior segment of the eye was strongly suspected. However, the long-term complication rate was high, the chief problems being tissue necrosis around the prosthesis with eventual prosthesis loss and the development of retroprosthetic membranes. Repeated replacements of keratoprostheses extruded or removed because of complications were possible with restoration of the vision obtained after the first implantation.

Keratoprosthesis. II. Results obtained after implantation of 27 dismountable two-piece prostheses. A retrospective, follow-up study.

During the years 1974-1987 a total of 27 two-piece keratoprostheses were implanted in 25 eyes of 22 different patients with bilateral blinding anterior segment disease with no possibility for a successful corneal transplantation. The prosthesis design and the surgical procedures used are described. The healing in and fixation of the prostheses were initially good in all cases, but 9 prostheses were lost or removed because of complications during the postoperative period of observation. The prosthesis retention time was significantly longer than that earlier achieved by the use of a one-piece prosthesis. In 18 of 27 cases a visual acuity of 6/60 or better was obtained. Postoperative complications included necrosis of the tissues covering and supporting the prosthesis, infection around the prosthesis, overgrowth of the surrounding tissues and the development of dense retroprosthetic membranes. Despite the obvious risks, keratoprosthesis surgery in a small number of patients with severe corneal disease represents the only potential hope for a visual rehabilitation, and should therefore be considered.

The prognosis of patients with hysterical visual impairment.

During the period 1962-1986, 54 patients received the diagnosis hysterical visual impairment, i.e. 1 out of every 631 patients admitted to our department. Isolated visual acuity impairment was the most common symptom, followed by combined visual acuity impairment and visual field constriction, whereas isolated visual field constriction occurred most infrequently. The mean age of the patients in the first group was significantly lower than that of the patients in the latter group. A questionnaire sent to all patients in 1987 was answered by 41 patients. Twenty-one of these (51%) felt that their visual function now was good, whereas 20 (49%) claimed that their visual function was still poor. Nine patients (22%) were disabled because of their visual problems. Twenty-nine of the patients who answered the questionnaire were re-examined. Sixteen of these (55%) still showed visual impairment at the follow-up, while 13 (45%) showed complete disappearance of visual complaints. The younger patients appeared to have a better prognosis than the older ones.

A new high precision fingertip controlled aspiration device for extracapsular cataract surgery.

The electronically foot-switch controlled irrigation/aspiration instruments have several disadvantages due to the big 'dead space' between the pump and the aspiration cannula. A new high precision fingertip controlled aspiration system is described. A specially designed ball valve connects the aspiration cannula directly to the vacuum reservoir, thereby almost eliminating the dead space. The system is nonelectric, it has no moving parts, it is easy to operate and highly cost efficient.