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Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. We are grateful to all the patients who have contributed to PsoProtect I Me i , the professional and patient organisations who supported or promoted PsoProtect I M i e and for the input of Prof Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Christine Janus and Ms Melissa Sweeney through their vital contributions. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. [Extracted from the article]

Summary: Background: Registry data suggest that people with immune‐mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID‐19) outcomes compared with patients receiving no systemic treatments. Objectives: We used international patient survey data to explore the hypothesis that greater risk‐mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk‐mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed‐effects model. Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk‐mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35–1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23–1·56). Shielding was associated with established risk factors for severe COVID‐19 [male sex (OR 1·14, 95% CI 1·05–1·24), obesity (OR 1·37, 95% CI 1·23–1·54), comorbidity burden (OR 1·43, 95% CI 1·15–1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27–1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36–1·80). Modest differences in the proportion shielding were observed across nations. Conclusions: Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence‐based patient communication on risk‐mitigation strategies and may help inform updated public health guidelines as the pandemic continues. What is already known about this topic? At the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, patients with immune‐mediated inflammatory diseases (IMIDs) on targeted systemic therapies were considered to be at higher risk of severe COVID‐19.Subsequent clinician‐reported registry data suggest that targeted systemic therapy use is associated with fewer adverse COVID‐19 outcomes compared with no systemic therapy. What does this study add? We characterize shielding behaviour in 3720 patients with IMIDs from a global self‐report survey.Use of targeted systemic therapy associates with increased shielding behaviour, compared with standard systemics or no therapy, as do demographic risk factors for severe COVID‐19 including male sex and obesity.Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes.Behaviour variation across treatment groups reinforces the need for clear, evidence‐based patient communication on risk‐mitigation strategies.These data may help to inform updated public health guidelines as the pandemic continues. Linked Comment: G. Becher and A.D. Burden. Br J Dermatol 2021; 185:7–8. [ABSTRACT FROM AUTHOR]

Introduction: For authors, selecting a target journal to submit a manuscript is a critical decision with career implications. In the discipline of medical education, research conducted in 2016 found that authors were influenced by multiple factors such as a journal's prestige and its mission. However, since this research was conducted the publishing landscape has shifted to include a broader variety of journals, an increased threat of predatory journals, and new publishing models. This study updates and expands upon how medical education authors decide which journal to submit to with the aim of describing the motivational factors and journal characteristics that guide authors' decision making., Methods: The authors conducted five qualitative focus groups in which twenty-two medical education authors and editors participated. During the focus groups participants were engaged in a discussion about how they select a journal to submit their manuscripts. Audio from all focus groups was transcribed. Transcripts were analyzed using codebook thematic analysis., Results: Participants considered multiple factors when selecting a target journal. Factors included a journal's impact, the scope of a journal, journal quality, and technical factors (e.g., word limits). Participants also described how social factors influenced their process and that open access plays a role that could both encourage or deter submission., Discussion: The findings describe the motivational factors and influential signals that guide authors in their journal selection decision making. These findings confirm, extend, and update journal selection factors reported in medical education and other disciplines. Notably, these findings emphasize the role of social factors, relationships and personal experiences, which were absent from previous work. Additionally, we observed increased consideration of open acces and a shift away from an emphasis on journal prestige., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited., Objectives: The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an 'as needed' approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care., Methods: We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on 'as needed' biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis., Results: Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of 'as needed' biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of 'as needed' drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9-64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8-33)]. Both patients and clinicians felt that an 'as needed' treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an 'as needed' approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence., Conclusions: These data indicate that 'as needed' biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized., Competing Interests: Conflicts of interest D.G. has received educational support from Lilly. L.M. has attended conferences, spoken at meetings and attended advisory boards for the following companies: AbbVie, Almirall, BMS, Janssen-Cilag, LEO, Lilly, Novartis, ONO Pharma, Pfizer and UCB. H.M. and G.S. are employed by the Psoriasis Association, which has received unrestricted educational grants over the past two years from Almirall, AbbVie, Janssen, Amgen, Eli Lilly, Dermal, UCB, LEO Pharma, Bristol Myers Squibb and Novartis. J.N.W.N.B. has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sienna, Sun Pharma and UCB. C.H.S. reports grants from a Medical Research Council-funded stratified medicine consortium with multiple industry partners (PSORT.org), grants from an IMI (Horizon 2020)-funded European consortium with multiple industry partners (BIOMAP-IMI.eu, HIPPOCRATES-IMI.eu, and others) and grants from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and Swedish Orphan Biovitrum, outside the submitted work; and is Chair of UK guidelines on biologic therapy in psoriasis. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Sanofi and UCB, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic., Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence., Methods: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence., Results: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49)., Conclusions: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes., Competing Interests: Conflict of interests J.W. has presented talks for Abbott, AbbVie, Bayer, Boehringer Ingelheim, Chiesi, Merck and Roche. K.J.M. reports personal fees from LEO Pharma and Novartis, outside the submitted work. H.M. reports grants from AbbVie, Almirall, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. D.U. reports grants from AbbVie, Almirall, Amgen, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. L.M. reports personal fees from AbbVie, Celgene, Janssen, LEO Pharma, Novartis and UCB, outside the submitted work. Additional disclosures from L.M. include Almirall, BMS and Lilly. H.B. reports personal fees from AbbVie, Almirall, Biocad, Boehringer-Ingelheim, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer and UCB, outside the submitted work. F.C. reports consultancy fees from AnaptysBio, grants from Boehringer Ingelheim, outside the submitted work. C.D.l.C. reports personal fees from Boehringer Ingelheim and UCB Pharma; grants from Janssen, Pfizer, Sandoz, Sanofi; grants and personal fees from AbbVie, Novartis, outside the submitted work. P.D.M. reports grants and personal fees from UCB; personal fees from Janssen and Novartis, outside the submitted work. P.G. reports personal fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz and UCB, outside the submitted work. D.J. reports personal fees and nonfinancial support from AbbVie, Celgene, Janssen-Cilag, Lilly, LEO Pharma, MEDAC and Novartis; and personal fees from Amgen, outside the submitted work. L.P. reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Lilly, Novartis and UCB; and personal fees from Bristol Myers Squibb, Fresenius-Kabi, Mylan, Pfizer, Samsung-Bioepis, Sandoz, Sanofi, outside the submitted work. P.S. has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid); has received departmental independent research grants for TREAT NL registry from pharma companies since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of diseases such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is chief investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children, as well as one of the main investigators of the SECURE-AD registry. T.T. reports grants and personal fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis and Sandoz, during the conduct of the study. R.B.W. reports grants from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO, Lilly, Medac, Novartis, Pfizer and UCB. R.B.W. also reports consultancy fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, LEO, Lilly, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. H.W. is on the Board of the International Federation of Psoriasis Associations who have received grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma and UCB, outside the submitted work. J.B.G. reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. C.E.M.G. reports grants and personal fees from AbbVie, Janssen, Lilly and Novartis and UCB Pharma; and grants from Almirall, Amgen, BMS, LEO and Pfizer, outside the submitted work. J.N.B. reports grants and personal fees from AbbVie, J&J, Lilly and Novartis during the conduct of the study. J.N.B. has attended advisory boards, and/or received consultancy fees, and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sun Pharma and UCB. C.H.S. reports grants from AbbVie, Novartis, Pfizer and Sanofi; and through consortia with multiple academic partners (psort.org.uk, BIOMAP-IMI.eu), outside the submitted work. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Novartis, Sanofi and UCB, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

This content analysis considered the San Francisco Homeless Project (SFHP), a collaboration of media organizations working to generate a wave of coverage to alleviate homelessness. The effort stood out for its proposed solutions to a systemic and complex issue involving multiple ecological levels of a community, the number and variety of organizations involved, and the ongoing nature of the project. Yet, little is known about its impact and potential for replication. Researchers coded 977 articles published by 134 media organizations over an 18-month period split into three phases (Preliminary, Wave 1, and Wave 2). Article frequency, characteristics, and content (code groups) were stratified by SFHP participation and described overtime. Results revealed that in addition to creating a media blitz, SFHP participants generated significantly longer and more visual articles and were influenced by nonprofits and government agencies. However, the SFHP did not lead to a sustained change in terms of article frequency and content., (© 2021 Wiley Periodicals LLC.)

In this article, we investigate the surge in use of COVID-19-related preprints by media outlets. Journalists are a main source of reliable public health information during crises and, until recently, journalists have been reluctant to cover preprints because of the associated scientific uncertainty. Yet, uploads of COVID-19 preprints and their uptake by online media have outstripped that of preprints about any other topic. Using an innovative approach combining altmetrics methods with content analysis, we identified a diversity of outlets covering COVID-19-related preprints during the early months of the pandemic, including specialist medical news outlets, traditional news media outlets, and aggregators. We found a ubiquity of hyperlinks as citations and a multiplicity of framing devices for highlighting the scientific uncertainty associated with COVID-19 preprints. These devices were rarely used consistently (e.g., mentioning that the study was a preprint, unreviewed, preliminary, and/or in need of verification). About half of the stories we analyzed contained framing devices emphasizing uncertainty. Outlets in our sample were much less likely to identify the research they mentioned as preprint research, compared to identifying it as simply "research." This work has significant implications for public health communication within the changing media landscape. While current best practices in public health risk communication promote identifying and promoting trustworthy sources of information, the uptake of preprint research by online media presents new challenges. At the same time, it provides new opportunities for fostering greater awareness of the scientific uncertainty associated with health research findings.

Journalists' health and science reporting aid the public's direct access to research through the inclusion of hyperlinks leading to original studies in peer-reviewed journals. While this effort supports the US-government mandate that research be made widely available, little is known about what research journalists share with the public. This cross-sectional exploratory study characterises US-government-funded research on cancer that appeared most frequently in news coverage and how that coverage varied by cancer type, disease incidence and mortality rates. The subject of analysis was 11436 research articles (published in 2016) on cancer funded by the US government and 642 news stories mentioning at least one of these articles. Based on Altmetric data, researchers identified articles via PubMed and characterised each based on the news media attention received online. Only 1.88% (n = 213) of research articles mentioning US government-funded cancer research included at least one mention in an online news publication. This is in contrast to previous research that found 16.8% (n = 1925) of articles received mention by online mass media publications. Of the 13 most common cancers in the US, 12 were the subject of at least one news mention; only urinary and bladder cancer received no mention. Traditional news sources included significantly more mentions of research on common cancers than digital native news sources. However, a general discrepancy exists between cancers prominent in news sources and those with the highest mortality rate. For instance, lung cancer accounted for the most deaths annually, while melanoma led to 56% less annual deaths; however, journalists cited research regarding these cancers nearly equally. Additionally, breast cancer received the greatest coverage per estimated annual death, while pancreatic cancer received the least coverage per death. Findings demonstrated a continued misalignment between prevalent cancers and cancers mentioned in online news media. Additionally, cancer control and prevention received less coverage from journalists than other cancer continuum stages, highlighting a continued underrepresentation of prevention-focused research. Results revealed a need for further scholarship regarding the role of journalists in research dissemination., Competing Interests: The authors have declared that no competing interests exist.

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited., Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization., Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors., Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94)., Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: The research sought to ascertain the types and quantity of research evidence accessed by health personnel through PubMed and UpToDate in a university medical center over the course of a year in order to better estimate the impact that increasing levels of open access to biomedical research can be expected to have on clinical practice in the years ahead., Methods: Web log data were gathered from the 5,042 health personnel working in the Stanford University Hospitals (SUH) during 2011. Data were analyzed for access to the primary literature (abstracts and full-text) through PubMed and UpToDate and to the secondary literature, represented by UpToDate (research summaries), to establish the frequency and nature of literature consulted., Results: In 2011, SUH health personnel accessed 81,851 primary literature articles and visited UpToDate 110,336 times. Almost a third of the articles (24,529) accessed were reviews. Twenty percent (16,187) of the articles viewed were published in 2011., Conclusion: When it is available, health personnel in a clinical care setting frequently access the primary literature. While further studies are needed, this preliminary finding speaks to the value of the National Institutes of Health public access policy and the need for medical librarians and educators to prepare health personnel for increasing public access to medical research.

Variations in intraocular pressure (IOP), observed by us and other authors in closed-system anterior chamber procedures, are explained using a simple hydrodynamic analysis based on the Bernoulli equation. Calculations show that the sudden increases in IOP (pressure spikes) measured during anterior segment surgery are due primarily to the small size of the infusion cannulas and are exacerbated by high infusion rates. Accurate measurement of these IOP variations requires placement of the pressure sensors in situ and is not possible by remote pressure sensing at the infusion line or the console. This work indicates that closed-system procedures could benefit from accurate monitoring of intraoperative IOP and could use these measurements for automatic IOP control during surgery.

The effectiveness of antimetabolic and anticollagen agents against proliferative vitreoretinopathy (PVR) was assessed by vitreous microtensiometry, a new technique that measures in situ the tensile strength of vitreous membranes. Two PVR models were produced in rabbits by intravitreal injection of bovine retinal pigment epithelial (RPE) or fibroblast cells, and the animals subsequently were treated with 5-fluorouracil (5-FU) and beta-aminopropionitrile (BAPN), administered alone or in combination. The fibroblast PVR model produced high-strength membranes that did not respond significantly to these therapies. The RPE model gave lower-strength membranes that showed marginally significant decreases in strength with intravitreal 5-FU and systemic BAPN treatments. However, combination therapy showed a highly significant decrease in membrane strength and a clinically encouraging reduction in retinal detachment.

This study assessed the effect of beta-aminopropionitrile treatment on the long-term curvature and compliance of corneal tissue subjected to radial keratotomy (RK). beta-Aminopropionitrile is known to inhibit cross-linking of collagen and is expected to enhance the flexibility of scar tissue, thereby reducing wound contracture and regression after RK. Seventeen adult New Zealand rabbits, weighing about 4.5 kg each, underwent RK in both eyes (eight incisions, 90% deep, 3-mm pupillary zone). Their mean preoperative corneal curvature was 44.25 diopters (+/- 0.32D at 95% confidence level). Nine of the rabbits were treated topically with beta-aminopropionitrile ointment (33 weight % in petroleum three times daily), while the control group received the petrolatum base only. The remainder of the animals received bland petrolatum gel as a control. The animals were given periodic keratometric examinations and were killed after six to eight weeks. At that time, the beta-aminopropionitrile group showed a mean reduction of 1.85 +/- 0.13 D in corneal curvature, compared with 1.18 +/- 0.08 D in the control group. The compliance and strength of the corneas were measured in vitro immediately after death. In the pressure range from 10 to 40 mm Hg, the beta-aminopropionitrile-treated corneas changed in curvature by an average of 1.4 D as compared with 0.5-D flattening for the controls. These results indicate the effectiveness of beta-aminopropionitrile treatment in enhancing longterm compliance and reducing refractive regression after RK.

Clostridiopeptidase A digested preretinal cicatricial tissue without causing morphological alteration of normal retina during a 30-minute incubation in the rabbit. Light and transmission electron microscopy were used to determine effects on the inner limiting membrane and retinal ganglion and Müller's cells and to evaluate enzyme digestion of preretinal scarring. Removal of the injected collangenase by vitrectomy resulted in normal electroretinograms and retinal morphology 48 hours postoperatively. If the enzyme was left in the eye for 24 hours, lens opacities, partial erosion of the inner limiting membrane, and extensive hemorrhage resulted. The specificity of action of the collagenase is due to the high degree of purity of the enzyme used and a substantial biochemical difference between scar collagen and basement membrane collagen. The injection of purified collagenase capable of digesting vitreal scar tissue while leaving the retina undamaged could represent a new approach to vitrectomy, specifically to facilitate certain cases of membranectomy.

Clostridiopeptidase A, a bacterial collagenase, was used to assist vitrectomy with membrane stripping in six patients with dense intravitreal fibroproliferative tissue associated with retinopathy of prematurity, diabetic retinopathy, or proliferative vitreoretinopathy. When it was injected intra-operatively, allowed to incubate for 15 minutes, and then removed by irrigation/aspiration, no side effects of lens opacity, lens dislocation, or retinal hemorrhage were observed. Use of this enzyme may facilitate removal of fibroproliferative tissue in certain difficult vitrectomy cases.

Beta-aminopropionitrile fumarate, an inhibitor of collagen cross-linking, was used topically in patients after filtration surgery for difficult cases of glaucoma (aphakic, repeat surgery, neovascular). Twenty-three patients received the drug for a total treatment period of three months following surgery. The mean preoperative intraocular pressure was 40.0 +/- 14.1 mm Hg (mean +/- standard deviation). The mean postoperative pressure was 19.0 +/- 8.9 mm Hg, with the mean follow-up at 26.4 +/- 11 weeks. The overall success rate was 74%, with success being defined as an intraocular pressure of 22 mm Hg or less at the last visit. Side effects consisted primarily of stinging immediately after the medication was applied. Inhibition of collagen cross-linking may represent an alternative method to the use of injectable 5-fluorouracil to maintain patency of filtration blebs.

Intravitreal irrigation with Balanced Salt Solution Plus (BSS Plus) produced less decrease in b-wave amplitude than either normal saline solution or Balanced Salt Solution. BSS Plus was more suitable for intravitreal irrigation because it contained the appropriate bicarbonate, pH, and ionic composition necessary for maintenance of normal retinal electrical activity, and it contained glutathione, which is necessary for maintenance of endothelial cell adenosine triphosphatase and for protection against free radical damage and oxidative stress.

Beta-aminopropionitrile, an inhibitor of collagen cross-linking, effectively limited the degree of posttraumatic vitreous proliferation in rabbits three weeks after double perforating injury. Light microscopic examination of the sites of perforating injury after five weeks showed minimal intravitreal fibrous proliferation in treated animals. Electron micrographs of the cicatricial vitreous collagen showed fragmentation of collagen into smaller fibrils and disintegration into amorphous areas. Inhibition of collagen cross-linking may undermine the strength of the vitreous scaffold by making vitreous and cicatricial collagen more sensitive to tissue collagenases produced during inflammation. The failure of fibrovascular membranes to grow into the vitreous may be a secondary effect of weakened vitreous support.

We studied the efficacy of a topical smooth muscle antagonist, thiphenamil hydrochloride (Trocinate), in inhibiting wound contraction in ocular tissue. Fifteen New Zealand white rabbits underwent standard eight-incision radial keratotomy (RK), and eyes were randomly assigned to treatment or control groups. As demonstrated by slit lamp corneal photographs and by ocular histology, transient inhibition of wound contraction lasted approximately one week in all treatment eyes. We conclude that thiphenamil has a temporary, but specific, effect in controlling wound contraction after ocular surgery. Smooth muscle antagonists may be useful for managing cicatricial conditions of the eye.

A light and electron microscopic study of an eye from a 79-year-old woman diagnosed as having sector retinitis pigmentosa is presented. Prominent bone spicule pigmentation was present bilaterally in the nasal quadrant. Retinal structure in the central fundus around the fovea and extending 2-3 mm peripherally was near normal with all photoreceptors and other retinal neurons present. Extensive degeneration of the retina occurred as one proceeded toward the peripheral regions from 3-5 mm from the fovea in all quadrants. Changes were evident within the entire choroid and were most severe in regions where retinal degeneration was most pronounced. It is likely that the extensive degenerative changes present in the retina were secondary effects that follow alterations in the choroidal blood supply in individuals affected with this disorder.

Electron microscopic analysis of intravitreal strands produced by the injection of autogenous fibroblasts showed thin, immature collagen after two weeks and the mature banded variety after four weeks. With the use of this intravitreal strand model, it was found that highly purified bacterial collagenase caused extensive digestion of scar tissue after incubation periods of 10, 15, and 30 minutes. There was no morphologic damage to cicatricial cellular elements or to the inner limiting membrane of the retina. A 45-minute exposure of retinas previously injured by photocoagulation to collagenase also did not result in morphologic evidence of damage. The use of collagenase as an adjunct to vitrectomy in cases of extreme vitreal scarring or retinal traction may decrease the complication rate of a procedure that is still extremely hazardous.

A method for the production of alkali-induced conjunctival scarring in rabbits with minimal corneal involvement is presented. The lathyritic agent Beta-aminopropionitrile (BAPN), an inhibitor of collagen cross-linking, was applied topically for a period of 21 days after induction of injury. There was a statistically significant (p less than .025) increase in both the interpalpebral fissure length and width of scarred treated animals compared with the scarred control group. BAPN did not affect the interpalpebral fissure measurements of unscarred rabbit eyes. No clinical adverse effects were observed after the treatment period. Histological evaluation of the treated scar tissue was consistent with lathyrism.