Journal Club 27-2-2021

Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

Thales Antonio Cabral de Guimaraes 1 2Michalis Georgiou 1 2James W B Bainbridge 1 2Michel Michaelides 3 2Affiliations expand

Free PMC article


Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections-even lifelong-and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results

John F Payne 1Charles C Wykoff 2W Lloyd Clark 3Beau B Bruce 4David S Boyer 5David M Brown 6TREX-DME Study GroupCollaborators, Affiliations expand


Background/aims: To evaluate the long-term effects of treat-and-extend dosing of ranibizumab with and without navigated focal laser for diabetic macular oedema (DME).

Methods: This is a multicentre, randomised clinical trial where 150 eyes were randomised into three cohorts; Monthly (n=30), TReat and EXtend without macular laser photocoagulation (TREX; n=60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n=60). During the first 2 years, eyes either received ranibizumab 0.3 mg every 4 weeks or underwent treat-and-extend ranibizumab with or without angiography-guided laser therapy. In the third year, all eyes were treated as needed with ranibizumab for >5 letters vision loss or if the central retinal thickness (CRT) was >325 µm, and all eyes were eligible to receive focal laser.

Results: 109 eyes (73%) completed the 3-year end-point. At week 156, mean best-corrected visual acuity (BCVA) and CRT improved by 6.9, 9.7, 9.5 letters (p=0.60) and 129, 138, 165 µm (p=0.39), in the Monthly, TREX and GILA cohorts, respectively. These improvements were reached prior to week 104 and no significant changes occurred from week 104 to week 156 (BCVA: p=0.34; CRT: p=0.36). The mean number of injections in the third year was 3.0, 3.1, and 2.4 in the Monthly, TREX and GILA cohorts, respectively (p=0.56). 86 eyes (79%) required at least one ranibizumab injection in the third year.

Conclusion: The improvements achieved after 2 years of treat-and-extend ranibizumab for DME were maintained in the third year with a mean of 3 intravitreal injections.

Trial registration number: FDA IND 119146, NCT01934556.

Long-term natural history of visual acuity in eyes with choroideremia: a systematic review and meta-analysis of data from 1004 individual eyes

Liangbo L Shen 1Aneesha Ahluwalia 1Mengyuan Sun 2Benjamin K Young 1Holly K Grossetta Nardini 3Lucian V Del Priore 4Affiliations expand


Background/aims: Best-corrected visual acuity (BCVA) is the most common primary endpoint in treatment trials for choroideremia (CHM) but the long-term natural history of BCVA is unclear.

Methods: We searched in seven databases to identify studies that reported BCVA of untreated eyes with CHM. We sought individual-level data and performed segmented regression between BCVA and age. For eyes followed longitudinally, we introduced a horizontal translation factor to each dataset to account for different ages at onset of a rapid BCVA decline.

Results: We included 1004 eyes from 23 studies. BCVA of the right and left eyes was moderately correlated (r=0.60). BCVA as a function of age followed a 2-phase decline (slow followed by rapid decline), with an estimated transition age of 39.1 years (95% CI 33.5 to 44.7). After the introduction of horizontal translation factors to longitudinal datasets, BCVA followed a 2-phase decline until it reached 0 letters (r2=0.90). The BCVA decline rate was 0.33 letters/year (95% CI -0.38 to 1.05) before 39 years, and 1.23 letters/year (95% CI 0.55 to 1.92) after 39 years (p=0.004).

Conclusion: BCVA in eyes with CHM follows a 2-phase linear decline with a transition age of approximately 39 years. Future trials enrolling young patients may not be able to use BCVA as a primary or sole endpoint, but rather, may need to employ additional disease biomarkers that change before age 39. BCVA may still have utility as a primary endpoint for patients older than 39 years who have measurable BCVA decline rates.

OCT-A characterisation of recurrent type 3 macular neovascularisation

Riccardo Sacconi 1 2Marco Battista 1 2Enrico Borrelli 1 2Alexandra Miere 3Eleonora Corbelli 1 2Vittorio Capuano 3Lea Querques 2Eric H Souied 3Francesco Bandello 1 2Giuseppe Querques 4 2Affiliations expand


Purpose: To investigate optical coherence tomography angiography (OCT-A) findings in recurrent type 3 macular neovascularisation (MNV).

Methods: In this retrospective cohort study, consecutive patients with type 3 MNV secondary to age-related macular degeneration underwent OCT-A at three different time points: baseline, after anti-vascular endothelial growth factor treatment with complete resolution of the exudative signs (ie, non-exudative stage) and at the recurrence of exudation (ie, recurrence stage). Demographics and clinical findings were analysed, including OCT-A features of type 3 MNV recurrence.

Results: Twelve eyes (12 patients, mean age 78±7 years) were included. Using OCT-A, at baseline all type 3 MNVs showed the presence of detectable flow downgrowing from the deep vascular complex (DVC) to the retinal pigment epithelium (RPE)/sub-RPE space. 6/12 eyes (50%) showed anomalous flow under the RPE, while the other 6 eyes showed flow reaching the RPE without anomalous flow in the sub-RPE space. At the non-exudative stage (after treatment), BCVA and CMT significantly improved (p=0.004 and p=0.036), and flow inside the retinal lesions reduced; interestingly the connection to the RPE/sub-RPE space regressed. At the time of recurrence, all type 3 MNVs showed the presence of intra/sub-retinal exudation with restoration of the flow deepening from the DVC to the RPE/sub-RPE space.

Conclusions: Detectable flow deepening from the DVC to the RPE/sub-RPE space using OCT-A is mandatory to have a new exudation secondary to recurrent type 3 MNV. Early detection of type 3 MNV recurrence by OCT-A characterisation may prompt retreatment and potentially prevent progression to late stages of the disease.

Retinal light sensitivity as outcome measure in recessive Stargardt disease

Maximilian Pfau 1 2Frank G Holz 1 3Philipp L Müller 4 3 5Affiliations expand


Background/aims: To evaluate the applicability of mesopic light sensitivity measurements obtained by fundus-controlled perimetry (FCP, also termed ‘microperimetry’) as clinical trial endpoint in Stargardt disease (STGD1).

Methods: In this retrospective, monocentre cohort study, 271 eyes of 136 patients (age, 37.1 years) with STGD1 and 87 eyes of 54 healthy controls (age, 41.0 years) underwent mesopic FCP, using a pattern of 50 stimuli (achromatic, 400-800 nm) centred on the fovea. The concurrent validity of mesopic FCP testing using the MAIA device (CenterVue, Italy), the retest variability and its determinants, and the progression of sensitivity loss over time were investigated using mixed-model analyses. The main outcomes were the average pointwise sensitivity loss in dependence of patients’ demographic, functional and imaging characteristics, the intrasession 95% coefficient of repeatability, and the pointwise sensitivity loss over time.

Results: Pointwise sensitivity loss was on average (estimate (95% CI)) 13.88 dB (12.55 to 15.21) along the horizontal meridian and was significantly associated with the electrophysiological subgroup, presence/absence of foveal sparing, best-corrected visual acuity and disease duration. The 95% coefficient of repeatability was 12.15 dB (10.78 to 13.38) and varied in dependence of the underlying mean sensitivity and local sensitivity slope. The global progression rate for the sensitivity loss was 0.45 dB/year (0.13 to 0.78) and was higher for the central and inner ETDRS subfields compared with more peripheral regions.

Conclusions: Mesopic light sensitivity measured by FCP is reliable and susceptible for functional changes. It constitutes a potential clinical outcome for both natural history studies as well as future interventional studies in patients with STGD1.

Prognostic value of intermediate age-related macular degeneration phenotypes for geographic atrophy progression

Sarah Thiele 1Jennifer Nadal 2Maximilian Pfau 3 4Marlene Saßmannshausen 3Monika Fleckenstein 3Frank G Holz 3Matthias Schmid 2Steffen Schmitz-Valckenberg 3Affiliations expand

Free PMC article


Background: To characterise early stages of geographic atrophy (GA) development in age-related macular degeneration (AMD) and to determine the prognostic value of structural precursor lesions in eyes with intermediate (i) AMD on the subsequent GA progression.

Methods: Structural precursor lesions for atrophic areas (lesion size at least 0.5 mm² in fundus autofluorescence images) were retrospectively identified based on multimodal imaging and evaluated for association with the subsequent GA enlargement rates (square-root transformed, sqrt). A linear mixed-effects model was used to account for the hierarchical nature of the data with a Tukey post hoc test to assess the impact of the local precursor on the subsequent GA progression rate.

Results: A total of 39 eyes with GA of 34 patients with a mean age of 74.4±6.7 (±SD) years were included in this study. Five precursor lesions (phenotypes 1-5) preceding GA development were identified: large, sub-retinal pigment epithelial drusen (n=19), reticular pseudodrusen (RPD, n=10), refractile deposits (n=4), pigment epithelial detachment (n=4) and vitelliform lesions (n=2). Precursor lesions exhibited a significant association with the subsequent (sqrt) GA progression rates (p=0.0018) with RPD (phenotype 2) being associated with the fastest GA enlargement (2.29±0.52 (±SE) mm/year.

Conclusions: The results indicate the prognostic relevance of iAMD phenotyping for subsequent GA progression highlighting the role of structural AMD features across different AMD stages.

Ocular toxoplasmosis: phenotype differences between toxoplasma IgM positive and IgM negative patients in a large cohort.

British Journal of Ophthalmology ( IF 3.611 ) Pub Date : 2021-02-01, DOI: 10.1136/bjophthalmol-2019-315522
Sofia Ajamil-Rodanes,Joshua Luis,Rabia Bourkiza,Benedict Girling,Angela Rees,Catherine Cosgrove,Carlos Pavesio,Mark Westcott

Purpose To investigate the differences in demographics and clinical characteristics of patients diagnosed with ocular toxoplasmosis according to their IgM status. Methods Retrospective case note analysis was carried out on patients who tested positive for serum Toxoplasma gondii -specific IgM antibodies (IgM+) as well as a comparator group who tested negative for serum IgM (IgM-), but positive for serum IgG. Patient demographics and clinical features were compared between the two groups to evaluate for any significant differences. Results One hundred and six patients were included in the study between March 2011 and June 2018, consisting of 37 in the IgM +group and 69 in the IgM- group. Patients in the IgM +group were significantly older (51.1 vs 34.1 years, p<0.0001), more likely to present with central macular lesions (32% vs 12%, p=0.012), and more likely to develop rhegmatogenous retinal detachment (11% vs 1%, p=0.049). In contrast, patients in the IgM- group were more likely present with pain (20% vs 3%, 0.017) and exhibit more severe inflammation of the anterior chamber and vitreous (p<0.05). Overall, retinal lesions were more likely to be superotemporal (55%) and superonasal (31%). Furthermore, age was associated with larger (p=0.003) and more peripheral lesions (p=0.007). Conclusions This study demonstrated significant differences in clinical characteristics of ocular toxoplasmosis according to serum IgM status. IgM+ patients were older, less likely to report pain, had lower levels of intraocular inflammation, but were more likely to have macular involvement. We also found age to be correlated with larger and more peripheral lesions.

Journal Club 20-2-2021


Diogo Cabral 1 2 3Florence Coscas 3 4Telmo Pereira 2Rita Laiginhas 5Catarina Rodrigues 1Catherine Français 3Vanda Nogueira 1Manuel Falcão 5Alexandra Miere 4Marco Lupidi 6Gabriel Coscas 3 4Eric Souied 4Affiliations expand


Purpose: To evaluate the correspondence between macular atrophy (MA) progression and Type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration.

Methods: Retrospective review of consecutive patients with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral domain optical coherence tomography, en-face near infra-red imaging and fundus autofluorescence. Macular neovascularization blood flow morphology was evaluated by swept-source optical coherence tomography-angiography. Qualitative features were categorized per ETDRS sector as: immature, mature; and hypermature pattern. An automatic analysis was designed in MATLAB coding language to compute MA per ETDRS. Measurements were compared between the baseline and the last follow-up visit.

Results: Twenty eyes from 20 patients were included; the mean age was 85.4 (8.3) years. The median follow-up was 1.85 (1.0-2.4) years and the median anti-vascular endothelial growth factor injection rate during follow-up was 4.0 (2.0-5.0) injections/year. During follow-up, sectors with persistence of an immature blood flow pattern had a lower MA growth rate than sectors with mature macular neovascularization flow patterns (P = 0.001).

Conclusion: The presence of an immature blood flow pattern on optical coherence tomography-angiography is associated with a lower progression rate of MA.


Pedro S Brito 1 2Jorge V Costa 1Catarina Barbosa-Matos 2 3Sandra M Costa 2 3Jorge Correia-Pinto 2 3Rufino M Silva 4 5 6Affiliations expand


Purpose: To study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti-vascular endothelial growth factor injections for diabetic macular edema (DME).

Methods: Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change < 10%, a CST change >20%, and a CST <330 µm, achieving an improvement ≥2 lines of visual acuity, achieving visual acuity ≥20/40.

Results: A significant improvement in CST and visual acuity was seen from third month onwards. Twenty-eight (48.1%) cases were classified as “early responders,” 24 (35.8%) as “late responders”, and 15 (22.4%) as “poor responders.” Serum vascular endothelial growth factor-A levels were significantly lower in “poor responders” (P = 0.006). C-reactive protein (hsCRP) was associated with a limited anatomic response (<10% CST change) (P = 0.002, OR = 1.845, cutoff value of hsCRP = 1.84 mg/L). hsCRP was also negatively associated with obtaining a final CST <330 µm (P = 0.04, r2 = 0.112, OR = 0.643). Baseline visual acuity was significantly associated with 12th month visual acuity (P < 0.001, r2 = 0.602) and also with an improvement ≥2 visual acuity lines (P = 0.009, OR = 20.54).

Conclusion: Increased high-sensitivity C-reactive protein was associated with limited anatomic response to anti-vascular endothelial growth factor treatment and persistent DME. Poor responders had significantly lower values of serum vascular endothelial growth factor-A, suggesting an alternative pathogenic pathway for persisting DME.


Mohamed Kamel Soliman 1Giampaolo Gini 2Ferenc Kuhn 3Barbara Parolini 4Sengul Ozdek 5Ron A Adelman 6Ahmed B Sallam 7European Vitreo-Retinal Society (EVRS) Endophthalmitis Study GroupAffiliations expand


Purpose: To evaluate the visual outcome associated with intravitreal antibiotics (IVA) and pars plana vitrectomy (PPV) for acute postprocedure endophthalmitis.

Methods: Data from 237 eyes presenting with acute postprocedure endophthalmitis were collected from 57 retina specialists in 28 countries. All eyes were treated with IVA on the day of presentation. We classified eyes according to the method of treatment used as IVA and early PPV (IVA + PPV within 1 week of presentation) groups.

Results: After exclusion of ineligible eyes, data from 204 eyes were analyzed. The mean (SD) age of patients was 62.7 (21.8) years and 69.3 (12.7) years in the IVA and PPV groups, respectively (P = 0.18). Endophthalmitis secondary to cataract, intravitreal injections, PPV, and other intraocular procedures represented 64.2%, 16.2%, 13.7%, and 5.9% of cases, respectively. Intravitreal antibiotics alone were administered in 55 eyes (27.0%), and early PPV was performed in 149 eyes (73.0%). No difference was found between groups in the final visual acuity of ≥20/60 (43.6%, 65 eyes vs. 34.5%, 19 eyes) and ≤counting fingers (30.9%, 46 eyes vs. 36.4%, 20 eyes) for IVA versus early PPV groups, respectively. Vision of light perception (odds ratio = 12.2; 95% confidence interval: 2.0-72.6) and retinal detachment (odds ratio = 7.7; 95% confidence interval: 1.5-409) at baseline were predictive of vision of ≤counting fingers. Retinal detachment at baseline (odds ratio = 20.4; 95% confidence interval: 1.1-372.1) was predictive of final retinal detachment status.

Conclusion: The current retrospective multicenter cohort of eyes with acute postprocedure endophthalmitis reports similar outcomes after treatment with IVA alone when compared with IVA and early PPV within 1 week of presentation.


Zhengyang Liu 1 2 3 4Luke A Perry 1Thomas L Edwards 2 3 4Affiliations expand


Purpose: Platelet count, mean platelet volume, platelet distribution width, and plateletcrit are standard indices of platelet activation that have been studied in retinal vein occlusion (RVO) and its subtypes: branch retinal vein occlusion and central retinal vein occlusion. This systematic review and meta-analysis aimed to assess the association between these platelet parameters and RVO.

Methods: We searched for studies investigating the association between these platelet indices and RVO in multiple online databases from inception to August 2020. Mean differences and the associated confidence intervals were obtained and calculated for each included study and pooled using random-effects inverse variance modeling. Meta-regression was used to explore interstudy and intrastudy heterogeneity.

Results: Thousand three hundred and twenty-five unique studies were screened, from which 24 studies encompassing 2,718 patients were included. Mean platelet volume and platelet distribution width were significantly elevated in RVO, with pooled mean differences of 0.45 fL (95% CI 0.24-0.66, P < 0.0001) and 1.43% (95% CI 0.57-2.29, P = 0.0011), respectively. Platelet count and plateletcrit were not significantly associated with RVO. Mean platelet volume was also independently elevated in branch retinal vein occlusion and central retinal vein occlusion.

Conclusion: Mean platelet volume and platelet distribution width are significantly elevated in RVO. Further research is required to explore the independence and potential prognostic significance of these associations.


Thibaud Mathis 1 2Célia Maschi 3Carlo Mosci 4Charlotte A Espensen 5Laurence Rosier 6Catherine Favard 7Sarah Tick 8Charles-Henry Remignon 1Paolo Ligorio 4Nicolas Bonin 9Joël Gambrelle 10Anh-Minh Nguyen 1Carsten Faber 5Laurent Meyer 11Frederic Mouriaux 12Joël Herault 13Stéphanie Baillif 3Jens-Folke Kiilgaard 5Laurent Kodjikian 1 2Jean-Pierre Caujolle 3Julia Salleron 14Juliette Thariat 15Affiliations expand


Purpose: The aim of this study was to compare the functional and anatomical effectiveness of photodynamic therapy (PDT) versus proton beam therapy (PBT) in a real-life setting for the treatment of circumscribed choroidal hemangioma.

Methods: A total of 191 patients with a diagnosis of circumscribed choroidal hemangioma and treated by PBT or PDT were included for analyses.

Results: The 119 patients (62.3%) treated by PDT were compared with the 72 patients treated by PBT. The final best-corrected visual acuity did not differ significantly between the two groups (P = 0.932) and final thickness was lower in the PBT compared with the PDT group (P = 0.001). None of the patients treated by PBT needed second-line therapy. In comparison, 53 patients (44.5%) initially treated by PDT required at least one other therapy and were associated with worse final best-corrected visual acuity (P = 0.037). In multivariate analysis, only an initial thickness greater than 3 mm remained significant (P = 0.01) to predict PDT failure with an estimated odds ratio of 2.72, 95% confidence interval (1.25-5.89).

Conclusion: Photodynamic therapy and PBT provide similar anatomical and functional outcomes for circumscribed choroidal hemangioma ≤3 mm, although multiple sessions are sometimes required for PDT. For tumors >3 mm, PBT seems preferable because it can treat the tumor in only 1 session with better functional and anatomical outcomes.


Enrico Borrelli 1Marco Battista 1Francesco Gelormini 1Maria C Gabela 1 2Flavia Pennisi 1Alberto Quarta 1Mario Pezzella 1Riccardo Sacconi 1Lea Querques 1Francesco Bandello 1Giuseppe Querques 1Affiliations expand


Purpose: To quantitatively evaluate the photoreceptor structural changes in the fellow unaffected eyes of patients with unilateral central serous chorioretinopathy (CSC).

Methods: This is a retrospective cross-sectional study. We analyzed data from patients with diagnosis of unilateral CSC, as based on clinical examination and multimodal imaging, who had structural optical coherence tomography obtained. An additional group of age-matched healthy patients was included for comparison. Main outcome measures were as follows: (1) the foveal photoreceptor outer segment lateral surface and (2) the foveal choroidal thickness.

Results: One hundred and sixty fellow unaffected eyes of 160 unilateral CSC patients and 50 age-matched controls (50 eyes) were included. The mean ± SD age was 51.6 ± 11.1 years (range 28-80 years) in the unilateral CSC group and 52.8 ± 10.8 years (range 31-74 years) in the control group (P = 0.511). The foveal photoreceptor outer segment lateral surface was significantly increased in the unaffected eyes with CSC in the fellow eye (0.068 ± 0.007 mm2) as compared with control eyes (0.060 ± 0.005 mm2, P < 0.0001). The mean ± SD foveal choroidal thickness was 368.0 ± 105.7 µm in the unilateral CSC group and 302.9 ± 92.2 µm in control patients (P < 0.0001). In the Pearson correlation test, the photoreceptor outer segment lateral surface correlated with the choroidal thickness in the CSC group (R = 0.166, P = 0.016) but not in the control group (R = -0.025, P = 0.864).

Conclusion: Our results corroborate the hypothesis that retinal and choroidal changes affect both eyes of patients with acute/history of unilateral disease. These structural changes could be intended as an imaging evidence of reduced photoreceptor outer segment turnover secondary to retinal pigment epithelium and choroid dysfunction.


Mirinae Kim 1 2Yeo Jin Lee 1Wookyung Park 1 2Young-Gun Park 1 2Young-Hoon Park 1 2Affiliations expand


Purpose: To identify the optical coherence tomography biomarkers that can collectively predict the probability of collapse or reduction of drusenoid pigment epithelium detachment (PED).

Methods: This consecutive observational case series reviewed the clinical data of 24 eyes with non-neovascular drusenoid PED. Among the study population, 17 eyes showed collapse or reduction of drusenoid PED. The mean follow-up duration was 44.8 ± 24.6 months. Optical coherence tomography-derived parameters were analyzed at baseline, at the last available visit before reduction of PED, at the first available visit after reduction of PED, and at the final visit.

Results: The mean subfoveal choroidal thickness showed a significant decrease after PED reduction and at the most recent visit (P = 0.015). Migration of retinal pigment epithelium cells was detected in 15 (88.2%) after PED reduction; however, there was no significance in the frequency of migration of retinal pigment epithelium cells at each time point (P = 0.392). Non-neovascular subretinal fluid was detected in 7 (41.2%) before PED reduction, 2 (11.8%) after PED reduction, and 2 (11.8%) at the final visit. Interestingly, subretinal fluid appeared more frequently just before reduction of PED (P = 0.029).

Conclusion: We found evidence of non-neovascular subretinal fluid and choroidal thinning before reduction in PED. This finding might be useful for detection and prediction of the progression of drusenoid PED.

Consecutive CNV in the Fellow Eye

Weekly Case Presentation 26-2-2021

Journal Club 13-2-2021

Special Thanks to Dr Amini and Dr Bazvand


Hossein Jamali 1Jamshid Eslami 2Farid Kalashipour 3Mohammad Hossein Nowroozzadeh 1Affiliations expand


Purpose: To evaluate the early effects of panretinal photocoagulation (PRP) on corneal sensation and dry eye signs in patients with diabetic retinopathy.

Methods: Fifty patients with Type 2 diabetes mellitus and very severe nonproliferative or non-high-risk proliferative diabetic retinopathy who required PRP for the treatment of their retinal condition were enrolled. All patients were treated using a pattern PRP device. Esthesiometry, tear breakup time test, Schirmer test, and corneal staining pattern were evaluated at baseline and 2 months after the last session of PRP.

Results: Data from 88 eyes of 50 patients (41 right eyes and 47 left eyes) were analyzed. The mean tear breakup time test (right eyes) was decreased from 9.51 at baseline to 7.66 seconds after PRP (P < 0.001). The post-PRP eyes showed more advanced grades of corneal staining than pre-PRP assessment (P < 0.001). The average value of Schirmer test was 14.39 versus 12.29 mm (without anesthesia; P < 0.001) and 8.17 versus 7.15 mm (with anesthesia, P < 0.001) for baseline versus post-PRP measurements, respectively. The corneal sensation also showed decrease after laser therapy (4.93 versus 4.31 cm; P < 0.001).

Conclusion: This study demonstrates that decreased corneal sensation and signs of dry eye are more common immediately after PRP for diabetic retinopathy. These conditions should be discussed with the patient preoperatively and managed postoperatively.


M Cristina Savastano 1 2Marco Rispoli 3Bruno Lumbroso 4Affiliations expand

Free PMC article


Purpose: To evaluate the incidence of neovascularization (NV) secondary to central serous chorioretinopathy (CSC)-a condition belonging to the spectrum of pachychoroid disorders by means of optical coherence tomography angiography.

Methods: One hundred and seventy five eyes with CSC were evaluated in this retrospective observational study. The eyes with acute or chronic CSC with no NV were included in Group 1, and those with NV were evaluated in Group 2. Only eyes that had undergone structural optical coherence tomography and optical coherence tomography angiography were included. Age, best-corrected visual acuity, and subfoveal choroidal thickness were evaluated in all eyes. In Group 2, the type and morphology of NV and the occurrence of exudation were considered.

Results: Of a total of 175 eyes with CSC, 86 had the acute form and 89 the chronic. Approximately 140 belonged to Group 1 (80%) and 35 to Group 2 (20%). Approximately 39.2% of all patient with chronic CSC developed NV. Mean age in Groups 1 and 2 was 53.3 years (±10.9) and 66.6 years (±10.2), respectively. Mean best-corrected visual acuity in Groups 1 and 2 was 45.7 (±11.7) and 30.9 (±17.9) early treatment diabetic retinopathy study letters, respectively. Mean CCT in Group 1 and 2 was 417.5 µm (±123) and 344.2 µm (±165.9), respectively. In Group 2, all patients had Type 1 NV (100%); 29 eyes (83%) had filamentous feature, and 6 eyes (17%) had irregular shape. Silent nonexudative NV was observed in 7 eyes (20%), all belonging to Group 2.

Conclusion: The use of optical coherence tomography angiography in everyday clinical practice allows for the accurate analysis of the chorioretinal vascular setting, with the identification of new vessels that could remain misdiagnosed.


Lea Dormegny 1Ludovic C Jeanjean 2Xuanli Liu 1 3Arnaud Messerlin 1Tristan Bourcier 1Arnaud Sauer 1Claude Speeg-Schatz 1David Gaucher 1Affiliations expand


Purpose: To assess the frequency of macular cysts (MCs) in retinal detachment treated with silicone oil and evaluate their impact on visual acuity and macular vascularization using optical coherence tomography-angiography.

Methods: Forty-three eyes of 41 patients treated with silicone oil for retinal detachment were retrospectively studied. Best-corrected visual acuity and 6- × 6-mm optical coherence tomography-angiography examination at least 3 months after silicone oil removal were reviewed. In eyes with MCs, cyst area was measured on the en face optical coherence tomography-angiography image using ImageJ. Density of superficial capillary plexus and area of superficial foveal avascular zone were generated by the optical coherence tomography-angiography. Density of deep capillary plexus and deep foveal avascular zone area were measured using ImageJ.

Results: Twenty-five eyes (58%) presented with MCs. Cysts were exclusively located in the inner nuclear layer in 60% of cases. Mean best-corrected visual acuity in the MC group was lower than that of the non-MC group (P = 0.012). Macular cyst area negatively correlated with best-corrected visual acuity (P = 0.0201). Density of superficial capillary plexus was higher in the MC group (P < 0.0001), whereas area of superficial foveal avascular zone was lower (P < 0.0001). Macular cyst area negatively correlated with density of deep capillary plexus (P < 0.001).

Conclusion: The incidence of INL-MCs after silicone oil removal is high. These are associated with impaired vision and macular vascular remodeling. We highlight their similarity with the “retrograde maculopathy” phenomenon.


Vilde M Thomseth 1David H Engelsvold 1Anastasia Ushakova 2Vegard A Forsaa 1Affiliations expand


Purpose: To explore the potentials of multicolor (MC) confocal scanning laser ophthalmoscopy (cSLO) to detect structural retinal pathology after macula-off rhegmatogenous retinal detachment (RRD) and to describe their appearances.

Methods: Thirty MC cSLO images of 30 eyes after RRD repair were prospectively studied for the presence of RRD-related pathology. All MC cSLO findings were verified using swept source optical coherence tomography. Positive percent agreements were calculated using swept source optical coherence tomography as reference.

Results: Eight RRD-related structural pathologies were identified and characterized: ellipsoid zone (EZ) disruption, foveal EZ rosette, outer retinal fold, retinal detachment line, subretinal fluid blebs, subretinal fluid layer, retinal striae, and intraretinal cysts. Multicolor cSLO positive percent agreements were as follows: EZ disruption: 79%, foveal EZ rosette: 73%, outer retinal fold: 67%, retinal detachment line: 84%, subretinal fluid blebs: 0.70%, subretinal fluid layer: 50%, intraretinal cysts: 60%, and retinal striae: 100%.

Conclusion: En face MC cSLO imaging detected and delineated RRD-related structural pathology in high agreement with cross-sectional swept source optical coherence tomography and can supplement optical coherence tomography in the documentation and monitoring of outer retinal remodeling processes after macula-off RRD. Foveal EZ rosette is a new finding of the foveal EZ.

Trial registration: NCT03187613.


Shane M Griffin 1H Richard McDonald 2 3Robert N Johnson 2 3J Michael Jumper 2 3Arthur D Fu 2 3Emmett T Cunningham Jr 2 3 4 5Lee Kiang 1Caleb C Ng 2 3Brandon J Lujan 1 2Affiliations expand


Purpose: To describe the appearance of concentric, fingerprint-like waves within the Henle fiber layer (HFL) using en face optical coherence tomography in patients with tractional pathologies of the retina.

Methods: Retrospective analysis of six eyes of six patients imaged by optical coherence tomography with volumetric slabs positioned at the level of the HFL.

Results: Optical coherence tomography data from six patients with tractional vitreoretinal pathology were reviewed. Concentric, fingerprint-like microwaves were visualized through en face optical coherence tomography in all six study eyes at the level of the HFL. This finding resembled the finding of HFL waves previously noted histopathologically from force exerted on this layer.

Conclusion: In retinal pathologies in which specific physical forces act on the retina, volumetric optical coherence tomography may permit visualization of en face concentric, fingerprint-like hyperreflective rings within the HFL. This “fingerprint sign” may represent a biomechanical consequence of traction on the retina and allow clinical decision making based on improved recognition of the existence of such traction.


David H W Steel 1Niall Patton 2Theodor Stappler 3Niral Karia 4Hans Hoerauf 5Nishal Patel 6Joachim Wachtlin 7Thomas Raber 8Petra Kozma-Wiebe 8INJECT study investigatorsAffiliations expand

Free PMC article


Purpose: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice.

Methods: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events.

Results: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events.

Conclusion: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

Punctate Outer Retinal Toxoplasmosis (PORT)

Weekly Case Presentation 9-2-2021

Journal Club – 2-6-2021

Journal Club – 2-6-2021 Special Thanks to Dr Fadakar and Dr Bazvand

2-2-2021 – Weekly Case Presentation

Special Thanks to Dr Ali Heidar – Dr Amin Nabavi – Dr Riazi