Introduction:
The benzoporphyrine derivative verteporfin has lost its importance to the treatment of the most frequent neovascular eye diseases. Nevertheless, it is still mandatory to define the ...remaining applications, role, and potential of verteporfin in ocular photodynamic therapy (PDT), including the dosages of administration, effectiveness, and safety profile.
Areas covered:
Although verteporfin PDT has forfeited the first-line status and value of treating subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration or pathologic myopia, the treatment remains the standard of care for choroidal haemangioma and polypoidal choroidal vasculopathy. PDT is effective in less pigmented choroidal melanoma as well as in retinal vascular proliferations and retinal angioma. Verteporfin was granted the orphan drug designation for the treatment of chronic or recurrent central serous chorioretinopathy (CSC).
Expert opinion:
Evidence-based data regarding optimized parameters (low fluence, reduced dose, fractionated irradiation) adapted to the treated diseases (target structure, dosimetry, blood supply) are scarce. Prospective and large clinical trials are missing, although the scientific community agrees on the fact that the standard treatment protocol does not necessarily provide the optimal efficacy to the specific disease or individual patient. Within the reviewed indications, the adverse effect profile is favorable compared with other therapies.
Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one ...eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear.
The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration.
This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used.
This took place in hospital eye services.
Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters.
The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography.
The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years.
In total, 552 out of 578 patients who consented from 24 NHS hospitals (
= 16 ineligible;
= 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval) was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9), fundus clinical examination 53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9), Amsler 33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5), visual acuity 30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1) and self-reported vision 4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5). Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities
-statistic 0.66 (95% confidence interval 0.62 to 0.71). Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored.
The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance.
Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye.
Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes.
This study was registered as ISRCTN48855678.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.
We investigated the performance of the handheld radial shape discrimination (hRSD) test in detecting the development of neovascular AMD (nAMD) in a prospective, longitudinal, observational study. ...Patients diagnosed with unilateral nAMD, with no nAMD in the other eye (the study eye, SE), completed the hRSD test on consecutive, routine clinic visits up to a maximum of 12, or until they were diagnosed with nAMD in the SE based on slit-lamp biomicroscopy and spectral-domain OCT assessment, with fluorescein angiography confirmation. Masked grading was carried out to confirm the diagnosis of nAMD, and to ensure no cases of nAMD were missed. Receiver operating characteristics (ROC) analysis was used to explore the diagnostic performance of the hRSD test relative to clinical diagnosis. Data were available from 179 patients of whom 19 (10.6%; "converters") developed nAMD in the SE. The mean hRSD threshold at conversion was -0.47 (95% CI -0.38 to -0.55) logMAR compared to -0.53 (-0.50 to -0.57) logMAR in 160 non-converters. hRSD threshold in the converters began to decline 190 days before diagnosis of nAMD. The ROC curve demonstrated that at an hRSD cut-off of -0.60 logMAR, sensitivity was 0.79 (0.54-0.94) with a specificity of 0.54 (0.46-0.62); positive and negative predictive values were 0.16 and 0.96 respectively. We conclude that the hRSD test has moderate sensitivity for detecting the earliest stages of nAMD in the at-risk fellow eyes of patients with unilateral nAMD, compared to clinical diagnosis. Given its relative inexpensiveness, ease of use and the inherent connectivity of the platforms it can be presented on, it may have a role in early detection of nAMD in the population at large.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed.
In 24 patients with choroidal melanoma (median diameter 5.85 mm), the ...exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors.
In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death.
Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year.
To describe the incidence, associations and outcomes of ocular surface squamous neoplasia (OSSN) in the United Kingdom.
Prospective, observational study of every new case of OSSN reported via the ...British Ophthalmological Surveillance Unit reporting scheme over a 12-month period. Cases were followed up for 12 months.
The reported incidence of OSSN was 0.53 cases/million/year (conjunctival intraepithelial neoplasia: 0.43 cases/million/year; squamous cell carcinoma: 0.08 cases/million/year). Eighty-five per cent of affected patients were male, 97% were Caucasian, and the mean age at presentation was 67.9 (±12.8) years. Information on potential underlying risk factors was frequently unknown. The most commonly affected sites were the limbus and the nasal and temporal bulbar conjunctivae. Most patients presented with a visual acuity of 6/9 or better, without symptoms of pain or visual loss. Excision (with or without additional treatment) was the most common first-line treatment and interferon (with or without additional treatment) was the most common second-line treatment, although management varied widely. Complications of treatment were rare but occasionally severe. Recurrence within 12 months of follow-up occurred in at least 6% of patients.
Although subject to reporting bias, these data suggest that there has not been a significant change in the incidence of OSSN in the United Kingdom, or its demographic profile, since 1996. The broad range of management approaches identified in this study reflect a lack of consensus as to the optimal referral and treatment pathways.
Background
Technological advances have led to cancer prognostication that is increasingly accurate but often unalterable. However, a reliable prognosis of limited life expectancy can cause ...psychological distress. People should carefully consider offers of prognostication, but little is known about how and why they decide on prognostication. Using uveal melanoma (UM) patients, we aimed to identify (i) how and why do people with UM decide to accept prognostication and (ii) alignment and divergence of their decision‐making from conceptualizations of a ‘well‐considered’ decision.
Methods
UM provides a paradigm to elucidate clinical and ethical perspectives on prognostication, because prognostication is reliable but prognoses are largely nonameliorable. We used qualitative methods to examine how and why 20 UM people with UM chose prognostication. We compared findings to a template of ‘well‐considered’ decision‐making, where ‘well‐considered’ decisions involve consideration of all likely outcomes.
Results
Participants wanted prognostication to reduce future worry about uncertain life expectancy. They spontaneously spoke of hoping for a good prognosis when making their decisions, but largely did not consider the 50% possibility of a poor prognosis. When pressed, they argued that a poor outcome at least brings certainty.
Conclusions
While respecting decisions as valid expressions of participants' wishes, we are concerned that they did not explicitly consider the realistic possibility of a poor outcome and how this would affect them. Thus, it is difficult to see their decisions as ‘well‐considered’. We propose that nondirective preference exploration techniques could help people to consider the possibility of a poor outcome.
Patient or Public Contribution
This paper is a direct response to a patient‐identified and defined problem that arose in therapeutic and conversational discourse. The research was informed by the responses of patient participants, as we used the material from interviews to dynamically shape the interview guide. Thus, participants' ideas drove the analysis and shaped the interviews to come.
To determine the outcomes of vitreoretinal surgery after choroidal tumor biopsy.
Retrospective, single-center, consecutive case series.
A total of 739 consecutive patients undergoing choroidal tumor ...biopsy.
All subjects who underwent transretinal or transscleral choroidal tumor biopsy for diagnostic or prognostic purposes between May 1993 and May 2013 were identified in our database. We then reviewed patients who subsequently required secondary vitreoretinal surgery for complications arising from such biopsies.
Reason for vitreoretinal surgery, association with biopsy procedure, best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution logMAR), intraocular or extrascleral tumor dissemination, resolution of vitreous hemorrhage, reattachment of the retina with a single vitreoretinal procedure, number of additional vitrectomies undertaken, and number of enucleations.
A total of 20 of 739 eyes (2.7%) underwent vitreoretinal surgery for complications arising from choroidal tumor biopsy. The tumors consisted of choroidal melanoma in all 20 eyes. The reasons for the secondary surgery included persistent vitreous hemorrhage in 1.9% (14/739), rhegmatogenous retinal detachment in 0.7% (5/739), and endophthalmitis in 0.14% (1/739). Median BCVA improved from 2.0 logMAR (mean, 1.92 logMAR; range, 0.8-2.7 logMAR) before vitrectomy to 0.72 logMAR (mean, 0.88 logMAR; range, -0.14 to 2.7 logMAR) after vitrectomy and 0.76 logMAR (mean, 1.14 logMAR; range, 0.1-3.0 logMAR) at the final visit (P < 0.0001, t test). Permanent resolution of vitreous hemorrhage was achieved in 6 of 14 patients, and reattachment of the retina was achieved in 2 of 5 patients after the first vitrectomy. A median of 1 (mean, 1.5; range, 1-3) additional vitrectomy was performed. Enucleation was necessary in 3 of 20 eyes (15%). There were no cases of intraocular invasion or extrascleral extension after vitrectomy.
Vitrectomy for complications of choroidal tumor biopsy is rare. Such corrective surgery is complex and is best undertaken by specialized ocular oncologists or vitreoretinal surgeons with experience in managing this problem.
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