Reper intraocular lens with artificial iris: implantation techniques and outcomes.

The authors describe the surgical techniques to implant a novel intraocular lens with artificial iris (Reper) in patients affected by traumatic aphakia and aniridia. Two surgical approaches are proposed: implantation by suture-loaded cartridge and "open sky" implantation combined with penetrating keratoplasty. The method of establishing the exact position of the scleral fixation points and the pre-assembly of the suture of Reper before its implantation are the main novel proposed surgical procedures. The rationale is to minimize surgical procedures in the anterior chamber and to prevent knot loosening and lens tilting. The simultaneous treatment of aphakia and aniridia with a single prosthesis, the stability of the Reper and the functional, anatomical and aesthetic outcomes obtained are the highlighted advantages in this study.

Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel-Lindau disease: an OCT and OCT angiography study.

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.

A new intraocular lens with artificial iris for treating a case of iris extrusion secondary to traumatic opening of a radial keratotomy.

PURPOSE: Traumatic globe rupture can lead to aniridia with subsequent glare, light sensitivity and psychological discomfort. The authors report the results of a sulcus implantation of a new intraocular lens with artificial iris (Reper) in an eye affected by traumatic opening of a radial keratotomy incision with total iris extrusion and subluxated cataract. METHODS: A case of 56-year-old female affected by aniridia and subluxated cataract in left eye secondary to a traumatic opening of one of 12 radial keratotomy underwent a Reper implantation with three-point transcleral fixation. The following parameters were collected at 1, 3 and 6 postoperative months: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT), simulated keratometry (Sim K), endothelial cell count (ECC) and anterior chamber depth (ACD). Pupil spread function study was performed to evaluate the high-order aberrations and the quality of vision. RESULTS: BCVA improved from light perception to 20/20 (Snellen fraction) at 6 postoperative months. No IOP postoperative peaks were detected. CCT was 520 µm at 6 postoperative months. Corneal topography showed regularization with symmetrical flattening of the central part and a residual peripheral curvature. No significant reduction of ECC was detected. ACD was stable, superior to 3 mm at each time point of follow-up. Pupil spread function study highlighted that the quality of vision was the same in both eyes at the end of follow-up. CONCLUSION: Reper is a promising functional and cosmetic solution for the treatment of aphakia and aniridia.

Quantification of vascular and neuronal changes in the peripapillary retinal area secondary to diabetic retinopathy.

PURPOSE: To investigate and quantify peripapillary vascular and neuronal changes secondary to diabetic retinopathy, using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN: This was a cross-sectional study. METHODS: 51 eyes of 51 patients affected by non-proliferative diabetic retinopathy (NPDR) and 19 age-matched healthy control eyes underwent full ophthalmic examination, including OCT and OCTA in the peripapillary area. Vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI) were quantified in a ring-shaped region of interest of each OCTA image. Capillaries and larger vessels were separately analysed. The thickness of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (GCC) was also analysed. RESULTS: VAD and VLF of peripapillary capillaries were significantly reduced in NPDR eyes, along with the progression of NPDR (p<0.05). VDI was significantly reduced in mild (p=0.0093) and moderate (p=0.0190) NPDR eyes, but not in severe NPDR (p=0.0841). Larger peripapillary vessels showed a significant increase of both VAD and VDI in NPDR eyes. pRNFL and GCC thickness decreased in NPDR eyes, reaching statistical significance only for GCC. No statistically significant correlation was found between perfusion parameters and pRNFL and GCC thickness. CONCLUSIONS: Retinal capillary remodelling in NPDR involves the peripapillary vascularisation too, as confirmed by OCTA quantitative parameters. The peripapillary macrovasculature and microvasculature need to be separately evaluated. The lack of direct correlation between peripapillary capillaries changes and the loss of retinal nerve fibres suggests that neuronal damage cannot be simply considered secondary to the microvascular one.

RETINAL VASCULAR ABNORMALITIES RELATED TO NEUROFIBROMATOSIS TYPE 1: Natural History and Classification by Optical Coherence Tomography Angiography in 473 Patients.

PURPOSE: To analyze and classify neurofibromatosis Type 1 (NF1)-related retinal vascular abnormalities (RVAs), their natural history and correlation with disease severity, in a large cohort of patients. METHODS: This was an observational longitudinal study with prospective enrollment. Four hundred and seventy-three patients affected by NF1 and 150 age-matched healthy subjects were consecutively enrolled. Retinal vascular abnormalities were detected by means of near-infrared reflectance and studied by optical coherence tomography angiography. The superficial vascular plexus and the deep vascular complex (DVC) were quantitatively and qualitatively analyzed. RESULTS: We identified RVAs in 82 of 473 (17%) NF1 patients, but in none of the 150 healthy subjects. A comparison revealed that NF1 patients with RVAs showed a higher number of NF1 diagnostic criteria (4.3 ± 1.5 vs. 3.9 ±1.5, respectively; P = 0.02) than patients without RVAs. Three different RVA types were identified on optical coherence tomography angiography: macrovascular angiomatosis of the sole superficial vascular plexus; macrovascular angiomatosis of the superficial vascular plexus combined with microvascular angiomatosis of the deep vascular complex; and combined macrovascular angiomatosis of both superficial vascular plexus and deep vascular complex. The prospective analysis of optical coherence tomography angiography images showed no significant longitudinal evolution of RVAs (mean follow-up: 3.7 ± 2.8 years). A single patient developed a de novo single RVA, and two RVAs showed detectable changes during follow-up. CONCLUSION: In NF1 patients, RVAs are a characteristic sign that correlates with a more severe systemic disease expression, usually remaining stable during time. Optical coherence tomography angiography allows for the identification of different RVAs subtypes.

Ocular Side Effects of EGFR-Inhibitor ABT-414 in Recurrent Glioblastoma: A Long-Term Safety Study.

This study aimed to prospectively evaluate, on a long-term basis, corneal side effects secondary to compassionate administration of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in patients affected by EGFR-amplified recurrent glioblastoma. Fifteen patients with a median follow-up of 4.3 months after treatment discontinuation were enrolled. Each patient underwent full ophthalmologic examination including in vivo corneal confocal microscopy (CCM). No CTCAE grade 4 toxicity and four (27%) grade 3 toxicities were documented during treatment. Ocular symptoms (blurred vision, eye pain, photophobia) were experienced by all patients, reaching maximal severity after the second ABT-414 infusion, with persistence until treatment discontinuation. During treatment, CCM documented specific changes in the corneal epithelium and in the sub-basal nerve plexus layer fibers of all eyes. The median time of symptoms resolution after treatment discontinuation ranged from 38 days (eye pain) to 53 days (photophobia). The median time of signs resolution ranges from 14 days (corneal ulcer) to 38 days (superficial punctate epitheliopathy, corneal stroma edema and intraepithelial cysts). ABT-414 corneal side effects are detectable in all treated patients. Related symptoms are gradually experienced by all patients during treatment and although reversible, they are characterized by a relative prolonged persistence after treatment discontinuation.

In vivo intraocular biomarkers: Changes of aqueous humor cytokines and chemokines in patients affected by uveal melanoma.

Inflammatory, angiogenic, and immune processes have been associated with uveal melanoma (UM). The aim of the present study was to evaluate the presence of some specific aqueous humor (AH) soluble biomarkers in eyes affected by UM. Thirty-five eyes affected by primary UM and 35 control eyes, scheduled for cataract surgery, underwent full ophthalmic examination and AH sampling at time of surgery (brachytherapy or cataract surgery, respectively). AH samples were analyzed by means of ELISA, to detect the concentration of selected cytokines, chemokines, and growth factors. Compared with the control group, higher levels of IL-6 (P = .049), IL-8 (P = .006), RANTES (P = .008), EGF (P = .032), bFGF (P = .016), MIF (P = .007), and MCP (P = .020) were detected in eyes with UM. VEGF concentration between the two groups was statistically borderline (P = .058). Comparison between clinical characteristics and cytokine concentrations showed a positive correlation between tumor thickness and IL-8 (P = .032), and degree of serous retinal detachment and IL-6 (P = .021). UM is characterized by the presence of retinal neuroinflammatory, angiogenic, and immune biomarkers in AH. The proteomic analysis of AH could characterize UM microenvironment, allowing to better understand its pathophysiology.

Corneal side effects induced by EGFR-inhibitor antibody-drug conjugate ABT-414 in patients with recurrent glioblastoma: a prospective clinical and confocal microscopy study.

BACKGROUND: The aim of this study was to prospectively analyse, for the first time worldwide by in vivo clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma. METHODS: Each enrolled patient underwent full ophthalmologic examination including in vivo CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it. RESULTS: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks. CONCLUSION: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.

IDENTIFICATION AND CLASSIFICATION OF MACULAR MORPHOLOGIC BIOMARKERS RELATED TO VISUAL ACUITY IN RADIATION MACULOPATHY: A Multimodal Imaging Study.

PURPOSE: To identify and classify, by a multimodal imaging approach, the most relevant macular morphologic biomarkers related to visual acuity in patients affected by radiation maculopathy secondary to brachytherapy. METHODS: Fifty-one consecutive patients previously treated with Iodine-125 brachytherapy because of uveal melanoma were enrolled. Each patient underwent full ophthalmologic examination including best-corrected visual acuity and multimodal macular imaging analysis. Macular morphological parameters were processed by a stepwise selection analysis. RESULTS: Three macular parameters were identified as the most relevant macular morphologic biomarkers of poor visual acuity: the vertical thickness of the thickest macular cyst (P = 0.0001), the presence of foveal inner segment/outer segment (IS/OS) layer disruption (P = 0.0054), and the presence of foveal retinal pigment epithelium atrophy (0.0884). The intergrader agreement for these morphologic biomarkers was 0.98, 0.92, and 0.92, respectively (interclass correlation coefficient). CONCLUSION: The vertical thickness of the thickest macular cyst, the presence of foveal retinal pigment epithelium atrophy, and IS/OS layer disruption can be used to clinically characterize radiation maculopathy. These parameters allow for separation of the edematous component of radiation maculopathy, which is potentially treatable in early disease stages, from late onset atrophic components, which are theoretically irreversible.

Uveal Melanoma Biopsy: A Review.

Intraocular tumor diagnosis is based on clinical findings supported by additional imaging tools, such as ultrasound, optical coherence tomography and angiographic techniques, usually without the need for invasive procedures or tissue sampling. Despite improvements in the local treatment of uveal melanoma (UM), the prevention and treatment of the metastatic disease remain unsolved, and nearly 50% of patients develop liver metastasis. The current model suggests that tumor cells have already spread by the time of diagnosis, remaining dormant until there are favorable conditions. Tumor sampling procedures at the time of primary tumor diagnosis/treatment are therefore now commonly performed, usually not to confirm the diagnosis of UM, but to obtain a tissue sample for prognostication, to assess patient's specific metastatic risk. Moreover, several studies are ongoing to identify genes specific to UM tumorigenesis, leading to several potential targeted therapeutic strategies. Genetic information can also influence the surveillance timing and metastatic screening type of patients affected by UM. In spite of the widespread use of biopsies in general surgical practice, in ophthalmic oncology the indications and contraindications for tumor biopsy continue to be under debate. The purpose of this review paper is to critically evaluate the role of uveal melanoma biopsy in ophthalmic oncology.

Peripapillary vascular changes in radiation optic neuropathy: an optical coherence tomography angiography grading.

AIMS: To investigate peripapillary vascular changes secondary to radiation optic neuropathy (RON) using optical coherence tomography angiography (OCT-A) and to propose a clinical grading of RON based on OCT-A findings. METHODS: Thirty-four patients affected by RON were consecutively included. Each patient underwent best corrected visual acuity measurement (ETDRS score) and OCT-A (Nidek RS-3000 Advance device, Nidek, Gamagori, Japan). The radial peripapillary capillary plexus (RPCP) and the entire peripapillary capillary bed (EPCB) were analysed. Quantitative analysis of the OCT-A images was performed using open-source available ImageJ software (National Institutes of Health, Bethesda, Maryland, USA). Qualitative analysis based on the proposed clinical grading (Grades 0-4) was also performed by two masked graders. RESULTS: RON clinical (qualitative) classification based on RPCP correlated with the quantitative RPCP perfusion analysis (P=0.0001). RON clinical classification based on RPCP statistically correlated with ETDRS score (P=0.001). RON clinical classification based on EPCB also correlated with the quantitative EPCB perfusion analysis and ETDRS score (P=0.02 and P=0.01, respectively). Compared with the clinical classification based on EPCB, the qualitative classification based on RPCP reached a higher intergrader agreement (0.96 and 0.86, respectively). CONCLUSION: OCT-A can be used to detect RPCP abnormalities and to clinically classify RON with a high interexaminer agreement. The proposed clinical classification is supported by the quantitative analysis based on the use of specific images elaboration techniques and correlates with visual acuity of the examined eyes.