Inferior rectus transposition as a secondary surgery in patients with acquired abducens nerve palsy.

We report the outcomes in 2 patients with acquired abducens nerve palsy with residual esotropia following superior rectus transposition and medial rectus recession who subsequently underwent inferior rectus transposition as a second procedure. Both patients showed improved abduction and reduced esotropia, with no induced cyclotorsion or vertical deviation. Inferior rectus transposition as a secondary procedure in these 2 patients with abducens nerve palsy appeared to augment the effect of prior superior rectus transposition and medial rectus recession.

Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report.

PURPOSE: To report and investigate proptosis in a young girl with Noonan syndrome. METHODS: Observational case report. RESULTS: A 16-year-old girl affected by Noonan syndrome underwent a complete ophthalmological examination showing bilateral proptosis with hypofunction of lateral rectus and superior oblique muscles. Visual acuity, color discrimination and fundus examination were unremarkable. The orbital MRI showed bilateral proptosis and symmetrical enlargement of extraocular muscles, with bellies thickening and tendon sparing. The young patient also complained restrictive hypertrophic cardiomyopathy. CONCLUSIONS: Proptosis is an uncommon ocular manifestation of Noonan syndrome and its pathophysiology has never been clarified. The MRI evidence of extraocular muscles enlargement associated with hypertrophic cardiomyopathy, led us to hypothesize a common altered pathway beneath these features, more specifically the MAP kinase pathway, since extraocular and cardiac muscles share a mesenchymal embryological origin.

RADIATION MACULOPATHY IS ANTICIPATED BY OCT HYPERREFLECTIVE RETINAL FOCI: A Large, Prospective, Confirmation Study.

PURPOSE: To investigate, by means of spectral domain optical coherence tomography, retinal reflectivity changes as an early biomarker anticipating radiation-induced macular edema (ME) in patients treated by iodine-125 (I-125) brachytherapy. METHODS: Thirty patients planned for I-125 brachytherapy because of uveal melanoma were prospectively included and followed every 4 months for five years. Reflectivity alterations, namely hyperreflective retinal foci, were characterized and counted by two independent masked examiners by means of spectral domain optical coherence tomography imaging. Hyperreflective retinal foci were defined as discrete intraretinal reflectivity changes ≤30 µm, with reflectivity similar to nerve fiber layer and without back shadowing. RESULTS: Macular edema occurred in 17 patients (24.2 ±15.1 months) (group 1) after irradiation. Thirteen patients showed no signs of ME at the 5-year follow-up (group 2). The number of hyperreflective retinal foci was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (P < 0.0001). In group 1, hyperreflective retinal foci at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P = 0.0002, r2=0.6129). The intergrader agreement was almost perfect (intraclass correlation coefficient = 0.80). CONCLUSION: Hyperreflective retinal foci may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy.

Thrombocytopenia as Type 1 ROP Biomarker: A Longitudinal Study.

This study aimed to prospectively evaluate the association between the appearance and evolution of retinopathy of prematurity (ROP) and selected blood parameters, focusing on platelets count. In total, 157 preterm consecutive babies screened for ROP were included and classified in: ROP necessitating treatment (group ROP1), ROP regressed without therapy (group ROP2) and no ROP (group no-ROP), divided in two phases for each group depending on gestational age. Blood parameters were weekly gathered and referred to postmenstrual age, ROP severity and phase. Platelet count mean values were statistically lower (p < 0.001) during both phases in ROP1 group (179 × 109/L vs. 213 × 109/L in phase 1 and 2, respectively) vs. other groups (ROP2: 286 × 109/L vs. 293 × 109/L; no ROP: 295 × 109/L vs. 313 × 109/L). Platelet count at birth <181 × 109 was statistically associated with Type 1 ROP development and evolution (sensibility = 76.47%, 95% confidence interval 60.0-87.6; specificity = 66.12%, 95% confidence interval 57.3-73.9). In ROP 1 group, a platelets count mean value "spike" (392.6 × 109/L) was documented at 36 weeks of corrected gestational age, preceding the need for treatment performed at a median of 38.1 ± 3.2 weeks. Early birth thrombocytopenia is confirmed as a biomarker of development and progression of ROP requiring treatment. The increase of platelets count at 35-37 weeks of corrected gestational age can be considered a possible clinical biomarker anticipating Type 1 ROP progression in preterm infants.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

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.