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Ophthalmology and Therapy Jan 2024The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration... (Review)
Review
The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100 mg/ml was 15.8 months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase 3 ARCHWAY trial reported that PDS with RBZ (100 mg/ml) refilled every 24 weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5 mg) in patients with nAMD over 9 months and 2 years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.
PubMed: 38055121
DOI: 10.1007/s40123-023-00843-5 -
Ophthalmology. Retina Feb 2024To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time...
Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial.
OBJECTIVE
To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial.
DESIGN
Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294).
PARTICIPANTS
Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage.
METHODS
A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year.
MAIN OUTCOME MEASURES
Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days.
RESULTS
Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016).
CONCLUSIONS
Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Diabetic Retinopathy; Angiogenesis Inhibitors; Microaneurysm; Prospective Studies; Treatment Outcome; Tomography, Optical Coherence; Biomarkers; Diabetes Mellitus; Recombinant Fusion Proteins; Receptors, Vascular Endothelial Growth Factor
PubMed: 37696393
DOI: 10.1016/j.oret.2023.09.004 -
International Medical Case Reports... 2023Development and spontaneous closure of a macular hole (MH) in a vitrectomized eye is relatively rare. We report our findings in a case in which vitrectomy was performed...
RATIONALE
Development and spontaneous closure of a macular hole (MH) in a vitrectomized eye is relatively rare. We report our findings in a case in which vitrectomy was performed successfully to treat a vitreous hemorrhage (VH), but a MH developed eight months later. The MH spontaneously closed 2 weeks later, but then reopened. A second vitrectomy was performed with insertion of the internal limiting membrane flap into the MH which led to the successful closure of the MH. The purpose of this article is to present an explanation of how MH developed in this eye without vitreous traction.
PATIENT
A 64-year-old woman visited an eye clinic with vision reduction in her right eye of 3 days duration. A VH was detected in the right eye and pars plana vitrectomy (PPV) was performed. A retinal tear was detected which was the origin of the VH. The vision was restored to a decimal visual acuity of 1.2. Eight months later, the patient noticed that her vision was distorted and was referred to our hospital.
DIAGNOSIS
Optical coherence tomographic (OCT) images showed a thin epiretinal membrane on the macula, cystoid changes in the macular area, and a full-thickness MH.
INTERVENTIONS
The MH closed spontaneously in two weeks, however a lamellar MH with an epiretinal proliferation (EP) developed 11 months later. Two months later, OCT showed cyst-like changes in the retina and a full-thickness MH. A second PPV was performed with the insertion of the ILM flap and EP into the MH to close the MH. Her visual acuity improved, and distorted vision was not present.
LESSONS
Clinicians should be aware that a MH can develop in a vitrectomized eye without vitreous traction but can close spontaneously. We conclude that careful follow-up examinations are necessary even in vitrectomized eyes.
PubMed: 37808920
DOI: 10.2147/IMCRJ.S429577 -
International Journal of Ophthalmology 2023To determine the incidence and predictive factors for epiretinal membrane (ERM) formation in eyes with complicated primary rhegmatogenous retinal detachment (RRD)...
AIM
To determine the incidence and predictive factors for epiretinal membrane (ERM) formation in eyes with complicated primary rhegmatogenous retinal detachment (RRD) tamponaded with silicone oil (SO).
METHODS
This retrospective case-control study included 141 consecutive patients with (51 eyes) and without (90 eyes) ERM formation after primary pars plana vitrectomy (PPV) and SO tamponade for complicated RRD. The risk factors for ERM were assessed using logistic regression analysis.
RESULTS
The prevalence of postoperative ERM was 36.2% (51/141). Multivariate logistic regression analysis showed that the risk factors for ERM in SO-tamponaded eyes included preoperative proliferative vitreoretinopathy [PVR; odds ratio (OR), 2.578; 95% confidence interval (CI) 1.580-4.205, <0.001], preoperative choroidal detachment (OR, 4.454; 95%CI 1.369-14.498, =0.013), and photocoagulation energy (OR, 2.700; 95%CI 1.047-6.962, =0.040). The duration of the preoperative symptoms, intraocular SO tamponade time, giant retinal tear, preoperative vitreous hemorrhage, preoperative best-corrected visual acuity, number of breaks, quadrants of RRD, axial length, and photocoagulation points were not predictive factors for ERM formation.
CONCLUSION
Preoperative PVR, choroidal detachment, and photocoagulation energy are risk factors of ERM formation after complicated RRD repair. Better ophthalmic care as well as patient education are necessary for such patients with risk factors.
PubMed: 37465504
DOI: 10.18240/ijo.2023.07.16 -
Cureus Apr 2024The ventricular migration of vitreous silicone oil (SiO) is rare and can easily be mistaken for intraventricular hemorrhage or a ruptured colloid cyst. We report here...
The ventricular migration of vitreous silicone oil (SiO) is rare and can easily be mistaken for intraventricular hemorrhage or a ruptured colloid cyst. We report here the case of an adult male who was misdiagnosed with a ruptured colloid cyst and was subsequently found to have ventricular migration of vitreous SiO. A 57-year-old male presented unresponsive following a respiratory arrest and underwent a head computed tomography (CT) scan that demonstrated multiple ovoid hyperdensities in the ventricular system, which was concerning for a ruptured colloid cyst. He was transferred to our institution for neurosurgical evaluation. Magnetic resonance imaging (MRI) was performed and demonstrated widespread abnormal diffusion restriction throughout the cortex and basal ganglia, consistent with anoxic brain injury secondary to hypoxic respiratory arrest. The MRI also demonstrated an abnormal signal in areas corresponding with the previously identified intraventricular lesions, which did not layer posteriorly. Given that the MRI sequence signals of the lesions in the ventricular system matched perfectly with the signals of the somewhat deflated SiO within the globe, these multiple ovoid lesions on imaging were most consistent with the migration of SiO from the vitreous body of the right globe into the ventricular system. This case demonstrates a diagnostic error that can occur in emergent settings because of the broad differential diagnosis for cerebral ventricular hyperdensities. A ruptured colloid cyst was considered the reason for transfer, with the anticipation of neurosurgical intervention, but further imaging demonstrated that this was an incidental finding in this patient who presented in extremis. Awareness of this rare clinical condition can prevent overutilization of resources and unnecessary interventions.
PubMed: 38738078
DOI: 10.7759/cureus.58043 -
Cureus Jul 2023Sickle cell disease (SCD) is a prevalent inherited blood disorder with various ocular manifestations, including sickle cell retinopathy (SCR), characterized by retinal...
Sickle cell disease (SCD) is a prevalent inherited blood disorder with various ocular manifestations, including sickle cell retinopathy (SCR), characterized by retinal microcirculation impairment and ischemic complications. We present the case of a 21-year-old male with sickle cell trait who experienced a sudden, painless loss of vision in his left eye. Ophthalmologic examination revealed vitreous hemorrhage and neovascularization, indicating SCR. Initial treatment with hydroxyurea and exchange transfusions led to partial improvement. However, due to persistent vitreous hemorrhage, the patient underwent a vitrectomy. The sickle cell trait affects a large global population, and its retinopathy is a rare but severe complication. The pathogenesis and risk factors for SCR are similar to those for SCD. The diagnosis of SCR is established through fundoscopic examination and graded based on Goldberg's classification. Management involves a multidisciplinary approach targeting systemic illness and visual defects, including hydroxyurea, photocoagulation, anti-vascular endothelial growth factors, and vitrectomy. Awareness, early diagnosis, and timely intervention are essential to preventing vision-threatening complications in sickle cell trait patients with SCR.
PubMed: 37637596
DOI: 10.7759/cureus.42535 -
PloS One 2023To evaluate the functional and structural outcomes as well as postoperative complications after pars plana vitrectomy (PPV) for severe features of proliferative diabetic...
Functional and structural outcomes and complications after pars plana vitrectomy for severe features of proliferative diabetic retinopathy in type 1 and type 2 diabetes mellitus.
PURPOSE
To evaluate the functional and structural outcomes as well as postoperative complications after pars plana vitrectomy (PPV) for severe features of proliferative diabetic retinopathy (PDR) in type 1 and type 2 diabetes mellitus (DM) patients.
METHODS
Twenty two eyes of type 1 diabetics (DM1 group) and 27 eyes of type 2 diabetics (DM2 group) were included. Best corrected visual acuity (BCVA), intraocular pressure (IOP), postoperative structural changes in optical coherence tomography (OCT) and postoperative complications such as recurrent vitreous haemorrhage, diabetic macular oedema, secondary glaucoma and persistent tractional retinal detachment (TRD) were assessed and compared between the two groups.
RESULTS
Complete reattachment of retina was achieved in 88.9% from the DM1 group and in 95.5% from the DM2 group and remained attached in follow-up. BCVA in DM2 group was significantly lower preoperatively (p = 0.04). Mean postoperative BCVA significantly improved in both studied groups, but it was more evident in eyes of type 2 diabetics compared to type 1 diabetics. In eyes in the DM1 group there was perceptible stabilisation of BCVA. Poor visual acuity or lack of improvement in BCVA in the DM1 group was related to preoperative subretinal haemorrhage in macular region, and TRD involving macula, whereas in the DM2 group-to preoperative subretinal haemorrhage and neovascular glaucoma. The postoperative structural changes (disruption of EZ and ELM) were observed more often in DM2 group, but had the greatest impact on BCVA in eyes of type 1 DM. Complications after PPV for PDR were rare and hadn't a significant influence on the final functional outcomes in both groups.
CONCLUSIONS
Functional improvement after PPV for severe features of proliferative diabetic retinopathy were more noticeable in patients with type 2 DM. Postoperative structural changes had more negative impact on BCVA in type 1 diabetics.
Topics: Humans; Diabetic Retinopathy; Diabetes Mellitus, Type 2; Vitrectomy; Retina; Retinal Detachment; Postoperative Complications; Retrospective Studies
PubMed: 37471387
DOI: 10.1371/journal.pone.0288805 -
Journal of Vitreoretinal Diseases 2023To report the clinical and anatomic outcomes of a single-stage rescue and sutureless 30-gauge needle-assisted transconjunctival intrascleral fixation of dislocated...
To report the clinical and anatomic outcomes of a single-stage rescue and sutureless 30-gauge needle-assisted transconjunctival intrascleral fixation of dislocated 3-piece rigid poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs). This retrospective noncomparative single-surgeon interventional study comprised eyes that had concurrent 23- or 25-gauge pars plana vitrectomy and IOL rescue with sutureless transconjunctival needle-assisted flanged haptic intrascleral fixation. Lamellar scleral dissection for haptic fixation was performed 3 mm posterior to the surgical limbus with 30-gauge needles. Primary endpoints included visual acuity (VA), IOL tilt measured with ultrasound biomicroscopy (UBM), and postoperative complications. The study evaluated 25 eyes of 24 patients. The IOL was successfully refixated in 24 of the 25 eyes. The mean preoperative logMAR VA of 1.21 ± 0.79 SD (median 1.3; Snellen equivalent 20/400) improved to 0.28 ± 0.35 (median 0.14; Snellen equivalent 20/30) postoperatively ( < .0001). The mean IOL tilt measured by UBM (n = 7) was 3.79 ± 3.60 degrees. The mean postoperative follow-up was 348 ± 284 days (range, 7-979 days). Postoperative complications included self-clearing vitreous hemorrhage (n = 9), retinal detachment (RD) (n = 1), cystoid macular edema (n = 3), and corneal edema (n = 3). Three eyes (13%) required additional surgery, 1 for RD and 2 for delayed haptic slippage and secondary IOL tilt causing irregular astigmatism. Intrascleral needle-assisted fixation of dislocated or mobile 3-piece PMMA IOLs is an effective, safe method to restore VA.
PubMed: 37706089
DOI: 10.1177/24741264231178377 -
Cureus Nov 2023Upadacitinib is a relatively new drug used to treat autoimmune diseases. However, patients treated with upadacitinib may develop infections. We report a case of...
Upadacitinib is a relatively new drug used to treat autoimmune diseases. However, patients treated with upadacitinib may develop infections. We report a case of cytomegalovirus (CMV) retinitis that developed during upadacitinib administration. A 79-year-old woman presented with progressively decreasing vision in both eyes. Her decimal best-corrected visual acuity (BCVA) was 0.2 in the right and 0.01 in the left eye. The patient was taking upadacitinib for one year. Fundus examination revealed vitreous opacities and extensive white retinal lesions with hemorrhage in both eyes. CMV was detected in the anterior aqueous humor, vitreous humor, and blood samples. We diagnosed her with panuveitis and CMV retinitis, performed a vitrectomy in both eyes, and administered intravenous ganciclovir and steroids. After treatment, her BCVA improved to 0.6 in the right and 0.1 in the left eye. Ophthalmologists and physicians should be aware of CMV infections in patients being treated with upadacitinib.
PubMed: 38060716
DOI: 10.7759/cureus.48337 -
Cureus Aug 2023Suprachoroidal hemorrhage (SCH) is an uncommon sight-threatening pathology, most often encountered intraoperatively. However, spontaneous presentation of SCH is even...
Suprachoroidal hemorrhage (SCH) is an uncommon sight-threatening pathology, most often encountered intraoperatively. However, spontaneous presentation of SCH is even rarer. We report the case of a 69-year-old diabetic patient with spontaneous SCH (SSCH) in her left eye masquerading as a vitreous hemorrhage. She developed treatment-resistant secondary angle-closure glaucoma. She was referred to the vitreoretinal team for intraocular exploration to identify the source of the hemorrhage. Pars plana vitrectomy identified extensive SCH intraoperatively. As far as the authors are aware, this is the first case in which the patient had such severe SSCH that the characteristic kissing choroidal sign was not visualized on repeated examinations and multimodal imaging. All initial evidence pointed towards a diagnosis of vitreous hemorrhage. This case demonstrates that if a patient has angle-closure glaucoma and persistently raised intra-ocular pressure that is treatment-resistant, then SCH is an important differential diagnosis to consider. Clinicians need to be aware of the risk factors of SCH, and early recognition with a timely intervention of SCH is important to optimize visual outcomes.
PubMed: 37664398
DOI: 10.7759/cureus.42817