The pathogenesis of retinal vein occlusion (RVO) is extremely complex and includes several mediators. These mediators represent potential drug targets that can be used in the development of ...intravitreal drugs.
PubMed/MEDLINE databases were accessed between April-May 2021 to find the most relevant scientific papers regarding drug targets and therapeutic implications in RVO, focusing on current therapeutic options and potential cornerstones of future advances in treatment.
Before the introduction of intravitreal therapies, the visual outcome following a diagnosis of RVO was extremely poor. Anti-VEGF and corticosteroid treatments have radically changed RVO prognosis, helping to preserve patients' visual function and their quality of life. According to current clinical data, anti-VEGF and corticosteroid drugs are associated with both pros and cons; the present recommendation is to employ anti-VEGF molecules as a first-line treatment. Advances in our understanding of the biomolecular characteristics of RVO offer a solid basis for the development of new therapeutic targets and treatments.
Occult Macular Dystrophy (OMD) is an autosomal dominant inherited retinal dystrophy caused by mutations in the retinitis pigmentosa 1-like 1 (RP1L1) gene. The present study describes a novel RP1L1 ...variant, identified for the first time in two Italian sisters diagnosed with OMD, along with multimodal imaging features, including Optical Coherence Tomography (OCT) Angiography.
We performed multimodal imaging including spectral-domain OCT, blue light autofluorescence (BAF), infrared autofluorescence (IRAF), swept-source OCT Angiography (OCTA), full-field and multifocal electroretinography. Genetic analysis was performed using Next-Generation Sequencing. Pathogenic potential of nonsynonymous novel variants was scored with two in silico algorithms.
Proband 1 (P1) and proband 2 (P2) were two Italian sisters of 61 and 56 years old. Both reported a history of progressive visual loss without fundoscopic alterations. P1 reported a 4-year history of rapid visual function worsening, and her best-corrected visual acuity (BCVA) was counting fingers in both eyes. P2 reported a 20-year history of mild but progressive visual acuity loss, and her BCVA was 1/10 and 2/10 respectively in her right and left eye. Structural OCT displayed disorganization of outer retinal bands at the macula and foveal cavitation; loss of foveal photoreceptors was remarkably evident on en-face OCT slabs. OCTA quantitative analysis found that vessel density was reduced both at SCP and DCP while choriocapillaris blood flow was relatively spared. Genetic analysis found the same rare dominant c.2873G > C, p.Arg958Pro variant in the RP1L1 gene. The substitution was regarded as moderately radical according to Grantham score while PolyPhen2 classified the amino acidic substitution as probably damaging.
Our study expands the mutational spectrum of RP1L1 gene: the rare c.2873G > C, p.Arg958Pro missense variant may be considered a new pathogenic variant for OMD, the first to be identified exclusively in an Italian family. Moreover, our quantitative OCTA data suggest that OMD is characterized by a rarefaction of superficial and deep capillary plexus.
Background:
Fluocinolone acetonide (FAc) implant represents a long-term strategy for the management of diabetic macular edema (DME). Because of the 3-year duration, the careful monitoring of the ...intraocular pressure (IOP) is necessary. The main aim of the study was to provide quantitative IOP cutoffs associated with the onset of IOP increases.
Methods:
The study was retrospectively conducted with 2-year of follow-up. We separately considered eyes with good IOP control (Group 1), eyes requiring IOP-lowering medications (Group 2) and eyes undergoing IOP-lowering surgery (Group 3). The statistical analysis assessed Delta% IOP changes over the 2-year follow-up. ROC analysis was performed to detect significant cutoffs associated with Group 2 and Group 3. IOP changes occurring after a previously administered dexamethasone (DEX) implant were also evaluated.
Results:
We included 48 eyes (48 patients), stratified as follows: Group 1 (25/48; 52%), Group 2 (19/48; 40%) and Group 3 (4/48; 8%). ROC analysis performed on IOP values detected 2-months later DEX implant showed a mean Delta IOP increase>24% significantly associated with IOP-lowering medications after FAc implant, whereas a mean Delta IOP increase>35% was significantly associated with IOP-lowering surgery after FAc implant. With respect to IOP changes occurred after FAc implant, our ROC analysis showed a mean Delta IOP increase>8% significantly associated with IOP-lowering medications, whereas a mean Delta IOP increase>15% was significantly associated with IOP-lowering surgery. DEX-related IOP changes showed 52% sensitivity and 100% specificity of FAc-related IOP increases.
Conclusions:
IOP changes provides clinically relevant cutoffs associated with the onset of FAc-related IOP increases.
To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA).
Observational, cross-sectional study.
...Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan.
Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2).
Fixation location and stability.
The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P < 0.01). Both PRL eccentricity and fixation stability were linearly associated with BCVA: every 1° increase in PRL eccentricity was associated with a 0.07 logarithm of the minimum angle of resolution (logMAR) worse BCVA (P < 0.0001) while every 1°2 increase in 95% BCEA was associated with a 0.01 logMAR worse BCVA (P < 0.001). No significant intereye correlation was found for PRL eccentricity and fixation stability, as well as no association between the patient's age and fixation parameters.
We demonstrated that most eyes affected by BVMD retain a central stable fixation and provided evidence that both fixation eccentricity and stability are strongly associated with visual acuity in BVMD. These parameters may serve as secondary end points for future clinical trials.
Proprietary or commercial disclosure may be found after the references.
To identify the vascular biomarkers of peripheral capillary nonperfusion in patients affected by naive central retinal vein occlusion (CRVO), and to analyze their changes over the follow-up.
...Consecutive prospective case series with a planned follow-up of 2 years.
Thirty-five patients affected by CRVO and 35 healthy gender- and age-matched subjects were enrolled in the study.
Ophthalmic examination included best corrected visual acuity (BCVA), ultrawidefield fluorescein angiography (UWFFA), OCT, and OCT angiography (OCTA).
Vessel density (VD) at the superficial capillary plexus and deep capillary plexus (DCP) were calculated on OCTA images. The ischemic index (ISI) was calculated on UWFFA.
The mean baseline ISI was 37%, increasing to 40% at the end of the follow-up, whereas it was 4.9% in the patients’ fellow eyes and 4.5% in the control group with no change over the follow-up. OCT angiography revealed VD reduction in the DCP, considering both 3 × 3 mm and 12 × 12 mm scans. The correlation analyses revealed that DCP VD was the only parameter showing a statistically significant correlation with the foveal avascular zone (FAZ) area, BCVA, and ISI.
Deep capillary plexus VD impairment is detectable in all CRVO cases, variably involving both the central retina (with enlarged FAZ) and the periphery (with VD reduction in the peripheral retina). The severity of DCP VD reduction has correlates with various clinical markers. Deep capillary plexus VD may represent a crucial biomarker to characterize CRVO, and further studies are necessary to identify the cutoff thresholds for the different clinical manifestations.
Proprietary or commercial disclosure may be found after the references.
Background:
To investigate optical coherence tomography angiography (OCTA) quantitative parameters associated with macular neovascularization (MNV) size modifications in age-related macular ...degeneration.
Methods:
Study design was prospective, with 1-year of follow-up. All the included MNV eyes were treated by anti-VEGF intravitreal injections. Quantitative OCTA parameters, including MNV vessel tortuosity (VT) and MNV reflectivity, were calculated. Post-hoc analyses assessed the correlation between quantitative OCTA metrics and MNV size modifications.
Results:
A total of 28 MNV eyes of 28 patients were included. Baseline LogMAR BCVA was 0.36 ± 0.21 LogMAR, improved to 0.28 ± 0.22 Log-MAR after 1-year (
p
< 0.01), with a mean number of 8 ± 3 anti-VEGF injections. Eyes characterized by high MNV VT values group showed worse outcome and higher increases of MNV size. A mean MNV reflectivity value of 101 was associated with a high probability of changes in MNV size. MNV growth was also influenced by the type of MNV, with type 2 and mixed type lesions showing increases in MNV size, unlike type 1 MNV. These factors showed a cumulative effect in determining MNV size modifications. In most of the cases, we observed MNV size increases. Conversely, MNV lesions characterized by low MNV VT values may experience size reductions over the follow-up (34% of cases). The number of intravitreal injections had no significant influence on MNV size changes.
Conclusions:
Quantitative OCTA allowed to discriminate highly perfused MNV lesions, providing a basis to predict MNV size modifications and the direction of MNV expansion.
To report optical coherence tomography angiography (OCTA) findings in patients affected by
-associated retinal dystrophies.
Patients affected by a genetically confirmed
-associated retinal dystrophy ...were prospectively enrolled in an observational study, along with age- and sex-matched healthy volunteers as control subjects. All study and control subjects received a complete ophthalmic examination and multimodal retinal imaging, including OCTA.
A total of 12 eyes from 6 patients were included in the study. The mean BCVA of patients was 0.42 ± 0.25 logMAR. Two patients showed large central atrophy, with corresponding definite hypo-autofluorescence on fundus autofluorescence (FAF). Another four patients disclosed different degrees of RPE mottling, with uneven FAF. On OCTA, the macular deep capillary plexus and choriocapillaris had a lower vessel density in eyes affected by
-associated retinopathy when compared to healthy controls. On the other hand, vessel density at the peripapillary radial capillary plexus, superficial capillary plexus, and deep capillary plexus was significantly altered with respect to control eyes. Statistical analyses disclosed a negative correlation between the deep capillary plexus and both LogMAR best corrected visual acuity and central retinal thickness.
Our study reveals that
-associated retinal dystrophies are characterized by vascular alterations both in the macular and peripapillary region, as assessed by OCTA.
Sclerochoroidal calcifications (SCC) are rare conditions characterized by unifocal or multifocal well-defined scleral deposits of calcium. The present study describes two cases of SCC complicated by ...the onset of choroidal neovascularization (CNV).
Five patients affected by SCC were enrolled in the study and two cases were complicated by CNV. Both patients underwent complete ophthalmic examination with multimodal imaging including optical coherence tomography angiography (OCTA).
In the two patients with CNV (1 male), BCVA was 20/40 and 20/50 in the affected eyes. Fundus examination revealed an irregular yellow-white lesion close to the superotemporal arcade in both patients, with exudation. The diagnosis of CNV was performed by means of fluorescein angiography in one patient and OCTA in the other patient. The patients received a total of 3 and 9 ranibizumab injections respectively over a six-year follow-up, reaching a final BCVA of 20/25 in both patients with stabilization of the CNV.
SCC may be complicated by CNV, with good management obtained by intravitreal anti-VEGF injections.
•Sclerochoroidal calcifications (SCC) are rare unifocal or multifocal well-defined scleral deposits of calcium.•Choroidal neovascularization (CNV) is an extremely rare complication of this disease.•We describe the multimodal imaging findings and the clinical management of two patients with SCC-related CNV responding to intravitreal ranibizumab treatment.
To identify different choroidal patterns in Stargardt disease (STGD) and to assess their clinical correlates.
100 STGD eyes (29 males; mean age 42.6 ± 16.5 years) and 100 control eyes (29 males; mean ...age 43.2 ± 8.5 years) were included. Optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained. Four different choroidal patterns, quantitative OCT and OCTA parameters were assessed and statistically analyzed. The main outcome was the correlation between each choroidal pattern and anatomical and functional retinal status. Furthermore, we assessed structural and best corrected visual acuity (BCVA) changes of each STGD subgroup after one-year.
Mean BCVA was 0.63 ± 0.44 LogMAR for STGD patients and 0.0 ± 0.0 LogMAR for controls (
< 0.01). All quantitative parameters appeared deteriorated in STGD compared to controls (
< 0.01). Choroidal patterns were distributed as follows: Pattern 1 (normal appearing choroid) (15%), Pattern 2 (reduced Sattler or Haller layer) (29%), Pattern 3 (reduced Sattler and Haller layers) (26%), Pattern 4 (Pattern 3 + choroidal caverns) (30%). More advanced patterns significantly correlated with a more severe loss of retinal structural integrity. Furthermore, only Pattern 3 and Pattern 4 showed remarkable signs of progression after one year.
Choroidal patterns were related with retinal structural status and BCVA loss, and with different disease progression.
To report a case of a patient affected by branch retinal vein occlusion (BRVO) showing a possible spontaneous retinal-choroidal anastomosis (RCA) at the level of the fovea.
A 72 years old male ...patient with diagnosis of BRVO of left eye (LE) one year before came to our observation for a follow-up visit.The patient underwent a complete ophthalmologic examination, including fluorescein angiography, structural optical coherence tomography (OCT), OCT-Angiography (OCT-A). Interestingly, OCT-A revealed the presence of blood flow suggestive of single collateral vessel descending from the deep capillary plexus up to and possibly below a hyperreflective subfoveal deposit.
We hypothesize that it can represent a RCA, starting from retinal capillaries and reaching the choriocapillary and choroidal vessels in order to allow a vascular shunt between the 2 circulations and thus a new passage for the blood flow. A similar condition is represented by laser-induced RCA for the treatment of non-ischemic central retinal vein occlusion in order to establish a new passage for the blood flow.
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