Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Ocular hypertension as a cause of cilioretinal artery obstruction in the young patient, about a case. / Hipertensión ocular como causa de obstrucción de arteria ciliorretiniana en el paciente joven, a propósito de un caso.

CLINICAL CASE: A 16-year-old patient seen in the Emergency Department due to loss of visual acuity (VA) in the left eye (LE), and oppressive headache of 1 day onset. The patient was on treatment with topical corticosteroids for viral conjunctivitis. The VA was 1.00 in the right eye and 0.05 in LE. The intraocular pressure was 42mmHg in both eyes. In the LE, the funduscopy revealed retinal ischaemic oedema in the papillomacular bundle. The optical coherence tomography angiography (OCT-A) showed an obstruction of the cilioretinal artery. The systemic study was normal, the cardiac and supra-aortic trunks ultrasound was normal, with ocular hypertension secondary to corticosteroids being the only causative agent identified. This case shows that in the event of an obstruction of the cilioretinal artery, a systemic study should be performed in order to identify possible embolic phenomena. Ocular hypertension is one of the possible causes that may be responsible for this condition.

Open angle glaucoma secondary to endogenous cortisone due to pituitary microadenoma in a young patient, a case report. / Glaucoma de ángulo abierto secundario a cortisona endógena por microadenoma hipofisario en un paciente joven, a propósito de un caso.

CASE REPORT: A 31-year-old male was referred for evaluation after being diagnosed with Cushing syndrome secondary to a pituitary microadenoma. He presented with a reduced visual acuity and high intraocular pressure (IOP) of 48mmHg in both eyes. The examination with biomicroscopy showed normal anterior segment, increased cup to disc ratio, and open angle. There was a moderate-advanced involvement in the visual field. The patient was diagnosed with glaucoma secondary to endogenous corticosteroids, and medical treatment was initiated pending the removal of the adenoma. The IOP did not return to normal after the incomplete removal of the adenoma, so a trabeculectomy was performed to control the IOP. As conclusions: In the case of an ocular hypertension with pituitary tumour, secondary glaucoma to endogenous cortisone should be suspected. Early treatment of the tumour is necessary to bring the cortisone and IOP levels back to normal. Late diagnosis or incomplete treatment of these tumours may lead to not obtaining adequate IOP control.

Agreement between Fourier-domain and swept-source optical coherence tomography used for optic nerve head measurements.

PURPOSE: To assess the correlation between optic nerve head measurements generated by Fourier-domain (FD) and swept-source (SS) optical coherence tomography (OCT) both in healthy Caucasian subjects and patients with primary open angle glaucoma (POAG). MATERIALS AND METHODS: This was a cross-sectional study of the right eyes of 118 subjects. In each participant, the measurements of disc area, cup to disc ratio (CDR), vertical cup to disc ratio (VCDR), rim area and rim volume were performed consecutively by FD-OCT and then SS-OCT. Participant age, gender and spherical equivalent were also recorded. Agreement between the two devices was assessed through intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: The study sample consisted of 95 healthy eyes and 23 eyes with glaucoma. Mean participant age was 48.6±20.0 years, 54.2% were female, and mean spherical equivalent was -1.6±3.0 diopters. FD-OCT and SS-OCT measurements were respectively: mean disc area 1.79±0.3 vs 1.83±0.3 mm2 (ICC=0.71), mean CDR 0.38±0.2 vs 0.33±0.2 (ICC=0.91), mean VCDR 0.58±0.2 vs 0.52±0.2 (ICC=0.92), mean rim area 1.05±0.4mm2 vs 1.03±0.5mm2 (ICC=0.29), and mean rim volume 0.14±0.11 vs 0.21±0.17mm3 (ICC=0.53). Good agreement between the devices was noted for rim area and rim volume in glaucoma subjects (ICC=0.76 and 0.68 respectively), while weak agreement was observed for these variables in healthy subjects (ICC≤0.50). CONCLUSIONS: The CDR and VCDR measurements provided by FD and SS OCT showed excellent agreement for the overall sample. When the devices were used for rim measurements, agreement was excellent only in the POAG patients.

Management of Wet Age-Related Macular Degeneration in Spain: Challenges for Treat and Extend Implementation in Routine Clinical Practice.

PURPOSE: To ascertain wet AMD (wAMD) management patterns in Spain. METHODS: A two-round Delphi study conducted through a questionnaire-based survey designed from literature review and validated by an independent Steering Committee. RESULTS: Forty-nine retina specialists experienced in wAMD participated by answering the two-round study questionnaire. Retina specialists are the main responsible for wAMD diagnosis and monitoring, including visits and associated procedures, with a median time per visit of 15 minutes. Standard treatment strategies are based on anti-VEGF administration, including standard loading dose administration followed by maintenance with aflibercept or ranibizumab (81% of patients). Although treat and extend (T&E) dosing strategy is considered as optimal for wAMD management (78% of the panelists), the main routine healthcare limitations (i.e., visits overload, reduced staff, short visit time, coordination issues, lack of facilities) conduct to self-defined "flexible" strategies, based on T&E and pro-re-nata (PRN) protocols. CONCLUSION: Proactive treatment patterns (T&E) are the preferred ones by the retina specialists in Spain. However, their proper implementation is difficult due to healthcare resource limitations, as well as organisation and logistic issues. The use of anti-VEGF agents with longer duration of action could facilitate the use of strict T&E approaches according to routine clinical practices.

Update on the usefulness of optical coherence tomography in assessing the iridocorneal angle. / Actualización de la utilidad de la tomografía de coherencia óptica para el estudio del ángulo iridocorneal.

The iridocorneal angle, due to its implications in the physiopathology of aqueous humour drainage, is a fundamental structure of the anterior chamber. Anterior segment optical coherence tomography is a rapid and non-invasive technique that obtains images in vivo. The high resolution allows it to analyse the normal anatomy of the angle, any alterations, and the changes that occur after different therapeutic interventions. Anterior segment optical coherence tomography technology has evolved to provide images that allow the identification and quantification of the angular structures in healthy subjects and in glaucoma patients, and especially the trabecular meshwork and the Schlemm's canal. It also enables the angle width to be quantified, with some objective parameters that have been standardised in recent years, such as the trabecular-iris angle, the angle opening distance, and the trabecular-iris area. This technique has multiple uses in the study of the different mechanisms of angle closure, the evaluation of changes after a laser peripheral iridotomy or iridoplasty after cataract surgery, as well as after the implantation of phakic lenses.

Incomplete posterior hyaloid detachment after intravitreal pegaptanib injection in diabetic macular edema.

PURPOSE: Posterior hyaloid adherences play a role in the pathogenesis of diabetic macular edema (DME). Intravitreal antivascular endothelial growth factor (VEGF) drugs are presently being used to treat DME. The authors report one case of incomplete posterior hyaloid detachment (PHD) following intravitreal pegaptanib to treat DME. This case shows a combined mechanism of DME resolution by anti VEGF and PHD. METHODS: Prospective, interventional, single case report. One male patient with bilateral DME was treated by intravitreal pegaptanib in his right eye every 6 weeks for 6 months (five injections) and followed for 42 months. RESULTS: Central macular thickness decreased from 511 to 376 microm at month 4 in the treated eye and remained within 10% of this value during follow-up. The posterior hyaloid became taut and partially detached after the third injection and was almost completely detached 1 year later. Visual acuity remained unchanged in both eyes during follow-up. CONCLUSIONS: PHD may play an important role in cases where macular thickness is successfully reduced or better acuity is achieved after intravitreal injections.

Effect of topical anesthetics on intraocular pressure and pachymetry.

PURPOSE: The determination of intraocular pressure (IOP) by noncontact tonometry (NCT) has been reported to be affected by central corneal thickness (CCT) and by the instillation of topical anesthetics. METHODS: In order to determine the influence of topical anesthetics on CCT and IOP measured by NCT, 80 eyes from 49 patients were examined before and after the instillation of topical anesthetics. RESULTS: Average age was 55.3 years (SD 18.4, range 18 to 93). Twenty-eight patients were female and 21 were male. Average basal IOP was 16.1 mmHg (SD 5.2, range 8 to 35.3). IOP was 14.8 mmHg (SD 4.6, 7.4 to 32.4) (p=0.0005, Student t test for paired data) 5 minutes after topical anesthetics instillation. CCT averaged 541 micronm (SD 32, range 482 to 604) before topical anesthetic drops and 541 micronm (SD 32, 490 to 607, p=0.89, Student t test for paired data) 5 minutes after topical anesthetics instillation. CONCLUSIONS: The study confirms that the instillation of topical anesthetics causes a reduction in IOP. These changes do not seem to be associated with changes in CCT.

Release hallucinations and visual loss as first manifestations of postoperative unilateral blindness.

PURPOSE: Release hallucinations (RH) with insight into the unreality of the hallucination have been reported in association with severe vision loss. Postoperative blindness following nonocular surgery may appear associated with central retinal artery occlusion (CRAO) caused by incorrect head positioning during surgery, intraoperative hypotension, and atherosclerosis. RH may initially mask the loss of vision. METHODS: Case report. RESULTS: A 27-year-old woman who had undergone lumbar spinal surgery for right L4-L5 discal herniation developed left eye visual loss and complex visual hallucinations immediately after surgery. Her symptoms were initially considered hallucinations related to the anesthesia and not taken into consideration until 4 days later. Ophthalmic examination disclosed CRAO probably caused by ocular compression during surgery. Optic nerve atrophy appeared during the following 6 years. CONCLUSIONS: Doctors and auxiliary personnel should be aware that visual hallucinations may be a sign of actual vision damage.

Intravitreal bevacizumab for adult-onset vitelliform dystrophy: a case report.

PURPOSE: Adult-onset foveomacular vitelliform dystrophy (AFVD) is often misdiagnosed as occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The authors report the anatomic and functional outcome of intravitreal bevacizumab in a case of AFVD associated with a suspected occult CNV. METHODS: Prospective, interventional, single case report. One female patient with decreased visual acuity (VA) and metamorphopsia secondary to AFVD received one single intravitreal injection of bevacizumab 1.25 mg. RESULTS: The patient reported unchanged VA and decreased metamorphopsia 6 weeks after the injection. Fluorescein angiography (FA) and optical coherence tomography (OCT) showed progressive decrease of subretinal fluid until complete disappearance. VA, OCT, and FA remained unchanged during 10 months follow-up. CONCLUSIONS: Intravitreal bevacizumab showed a morphologic improvement and stable VA in a patient with AFVD. Further case series are required to confirm this observation.

Update of choroidal imaging techniques: Past, present and future. / Actualización en técnicas de imagen coroidea: pasado, presente y futuro.

The choroid is the middle layer of the eye, a very vascular and pigmented tissue, with its role in several ophthalmological pathologies already having been clearly established. But it was not until the last few years that we have been able to reliably and precisely measure and quantify its shape and thickness. Ultrasound technology and indocyanine green angiography were the first techniques used for the study of the choroid, and they still maintain their use and clinical indications for the diagnosis and management of several pathologies. But it was the advent of optical coherence tomography that was the greatest breakthrough in choroidal imaging. In this chapter, the past, current and future image modalities for the study of the choroid will be discussed, with special focus on optical coherence tomography and its latest developments.

Triamcinolone and PDT to treat exudative age-related macular degeneration and submacular hemorrhage.

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin and intravitreal injection of triamcinolone to treat choroidal neovascularization (CNV) with flat sub-macular hemorrhage in age-related macular degeneration (ARMD). METHODS: A prospective, consecutive, noncomparative, interventional case series study was performed at the Instituto Oftalmologico de Alicante, Spain. Ten consecutive eyes from 10 patients with flat submacular hemorrhage secondary to ARMD were treated by PDT followed by intravitreal injection of 19.4+/-2.1 mg/0.1 mL triamcinolone 5 days later. PDT was repeated if leakage from the CNV appeared on fluorescein angiography (FA) at 3 months follow-up intervals. Main outcome measures were best-corrected visual acuity (BCVA) before and after treatment, post-treatment FA, results, and complications. RESULTS: Stable or improved BCVA was achieved in seven eyes at 6 months follow-up. Complete absence of leakage in FA was observed in five and in eight eyes at 3 and 6 months follow-up, respectively. Intraocular pressure rose in seven eyes. CONCLUSIONS: PDT followed by intravitreal triamcinolone seems useful to treat CNV with flat submacular hemorrhage in ARMD. However, further studies with longer follow-up and randomized controlled trials are necessary to assess its efficacy in the management of this difficult clinical problem.

Phacoemulsification in the vitreous cavity for retained nuclear lens fragments.

PURPOSE: To evaluate anatomic and functional results after surgery of retained lens fragments in the vitreous cavity after previous phacoemulsification. METHODS: The authors studied retrospectively 18 patients who underwent pars plana vitrectomy (PPV) for retained nuclear lens fragments. Patients having only cortical material in the vitreous cavity were excluded. In all cases the nucleus or nuclear fragments were removed after a complete vitrectomy using perfluorocarbon injection in the vitreous cavity, associated with phacoemulsification in the vitreous cavity. The authors used a conventional phaco probe devoid of the silicone sleeve. Time lapse between cataract surgery and vitrectomy varied between 0 and 24 days (mean 8.2 +/- 7.4). Follow-up was 33.9 +/- 20.6 months (range 4 to 53). RESULTS: The mean final best-corrected visual acuity (BCVA) was 20/45 (range 20/400 to 20/20). It was 20/40 or better in 33% of patients, reaching 40% when patients with previous macular disease were excluded. A total of 61% of patients reached a final BCVA ranging from 20/50 to 20/200. Retinal detachment occurred in one eye and topical medications were necessary to manage intraocular pressure in four cases. CONCLUSIONS: PPV with intravitreous phacoemulsification is the technique of choice for dislocated nuclei or nuclear fragments in the vitreous cavity. (

Endogenous endophthalmitis by Propionibacterium acnes associated with leflunomide and adalimumab therapy.

PURPOSE: To report a case of unusual endogenous endophthalmitis associated with the use of leflunomide and adalimumab. METHODS: A 48-year-old woman on treatment with leflunomide and adalimumab for rheumatoid arthritis developed an endogenous endophthalmitis caused by Propionibacterium acnes. Diagnosis was confirmed by polymerase chain reaction and positive cultures. The patient underwent surgical treatment and intravitreal vancomycin, but the eye developed retinal fibrosis and untreatable retinal detachment. RESULTS: This report of endogenous endophthalmitis associated with the use of anti-tumor necrosis factor alpha (anti -TNF-a) drugs is consistent with those in the literature. P. acnes may induce pathologic reactions in compromised patients and cause endophthalmitis, but only after ocular surgery or in intravenous drug users. The Naranjo probability scale indicated a probable relationship between the drugs and the infection. CONCLUSIONS: Awareness of atypical infectious conditions in patients on anti-TNF-a drugs is critical for early diagnosis and good outcome.

[Variation of central corneal thickness in diabetic patients as detected by ultrasonic pachymetry]. / Variación del espesor corneal central en pacientes diabéticos mediante paquimetría ultrasónica.

OBJECTIVE: To prove the existence of a correlation between central corneal thickness and diabetes. METHODS: Ultrasound pachymetry measurements were made in 1,000 patients. The sample was divided into two groups of patients: 953 of them were non-diabetic patients, and 47 were diabetic patients. RESULTS: The average central corneal thickness in diabetic patients was 571.96 +/- 26.81 microns with a range between 514 and 626. The average central corneal thickness found in non-diabetic patients was 544.89 +/- 35.36 microns with range of 448 to 649. The increase in central corneal thickness found in diabetic patients compared to non-diabetic patients was statistically significant (p<0.001, Student "t" test). CONCLUSIONS: We found that diabetic patients had an increased central corneal thickness when compared with non-diabetic patients.

Cost of myopic patients with and without myopic choroidal neovascularisation. / Costes en pacientes miopes magnos con y sin neovascularización coroidea miópica.

OBJECTIVE: To study the costs associated with high myopia (HM) with choroidal neovascularisation (mCNV) or without mCNV. METHODS: Observational, retrospective, cross-sectional, and multicentre study (HM and mCNV) conducted on adult patients. Annualised medical direct cost (MDC) from the perspective of the National Health System, the non-medical direct cost (nMDC) from the patient perspective, and productivity losses were calculated. RESULTS: A total of 137 mCNV and 48 HM patients were included (mean age [SD]: 55.1 [2.8] vs. 54.7 [13.8]; P=.2), with 80% women in both groups. The observation time (months) ranged from 17.9 (9.6) right eye (RE) and 20.0 (9.7), left eye (LE) in mCNV and 47.1 (21.5) RE/45.5 (20.7) LE in MM. A higher percentage of emergency room visits was observed in mCNV vs. HM patients (41.7 vs. 25%; P=.06) and retinal specialists (91.2 vs. 77.1%; P=.01). The MDC was higher in mCNV: € 1,985 (95% CI: 1772-2198) vs. € 356 (251-480) HM, P<.001. The nMDC was also higher in mCNV: € 256 (11-524) vs. €19 (11-26) HM, P>.4. The number of affected eyes, the follow-up time, and the mCNV were factors associated with direct costs. The impact on work productivity was higher in mCNV (quite/very concerned): 27.7 vs. 10.4% HM. The mCNV showed a significant association with activity impairment (OR: 3.47, 95% CI: 10.101-1.195). CONCLUSIONS: mCNV involves higher medical costs than HM. In addition, mCNV patients have a greater need of care and assistive devices, and greater impact of the disease in their work productivity.

Optical coherence tomography characterisation of idiopathic central serous chorioretinopathy.

AIM: To describe retinal findings in patients with idiopathic central serous chorioretinopathy (ICSC) as assessed by optical coherence tomography (OCT), and to compare them to fluorescein angiography (FA) findings. METHODS: Case series of 39 eyes from 36 patients with ICSC. Complete ophthalmological examination, last generation OCT (StratusOCT, Software version 3.1) and FA were performed. Six radial scans using OCT were performed and repeated. Singular findings were recorded, OCT images were measured and the results compared with those of FA. The main outcome measures were FA and OCT findings. RESULTS: Two patterns of distinct OCT findings are described. In the first one, an optically empty vaulted area of different heights was observed under the neurosensory retina in 36 eyes, being related to fluorescein filled areas; in 35 of them, highly characteristic small bulges could be observed protruding from the retinal pigment epithelium (RPE), angiographically related to leaking spots. In the second pattern, three eyes showed an almost semicircular space under the RPE, with thinner overlying retina. CONCLUSIONS: OCT may offer a new approach to the staging and knowledge of ICSC, and may help the understanding of the mechanisms of the disease.

Vitreoretinal surgery for macular hole after laser assisted in situ keratomileusis for the correction of myopia.

UNLABELLED: AMS: To describe the characteristics and surgical outcomes of full thickness macular hole surgery after laser assisted in situ keratomileusis (LASIK) for the correction of myopia. METHODS: 13 patients (14 eyes) who developed a macular hole after bilateral LASIK for the correction of myopia participated in the study. RESULTS: Macular hole formed 1-83 months after LASIK (mean 13 months). 11 out of 13 (84.6%) patients were female. Mean age was 45.5 years old (25-65). All eyes were myopic (range -0.50 to -19.75 dioptres (D); mean -8.4 D). Posterior vitreous detachment (PVD) was not present before and was documented after LASIK on 42.8% of eyes. Most macular hole were unilateral, stage 4 macular hole, had no yellow deposits on the retinal pigment epithelium, had no associated epiretinal membrane, were centric, and had subretinal fluid. The mean diameter of the hole was 385.3 microm (range 200--750 microm). A vitrectomy closed the macular hole on all eyes with an improvement on final best corrected visual acuity (VA) on 13 out of 14 (92.8%) patients. CONCLUSIONS: This study shows that vitreoretinal surgery can be successful in restoring vision for most myopic eyes with a macular hole after LASIK.