A case of lung poorly differentiated squamous cell carcinoma-associated retinopathy

To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti-vascular endothelial growth factor (VEGF) treatment with Ranibizumab. A consecutive series of 39 study eyes with centre-involving DME were included in this study. In all subjects, best-corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD-OCT) cross-sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross-sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = -1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = -3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = -4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = -1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = -0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = -2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti-VEGF therapy with Ranibizumab in patients with DME.

BackgroundRGS9 (Regulator of G protein Signaling 9) encodes a protein that deactivates G proteins in phototransduction. Pathogenic variants in RGS9 have been described in association with bradyopsia (‘slow vision’), manifesting...

To assess the interobserver variability (IOV) in indicating retreatment for neovascular Age-related macular degeneration 4 weeks after three Ranibizumab loading doses using spectral domain OCT (SD-OCT) as the primary objective diagnostic tool. Four observers decided for or against 4th Ranibizumab injection in 108 patients by six different rating rounds (RR) based on the SD-OCT findings after the loading doses. Postoperative OCT images were supplemented consecutively with information from a chart review as the 'patients subjective estimation of vision (SE)', the course of best-corrected visual acuity (BCVA) and the preoperative OCT as well as all information collectively. Agreement rates (AR) and Kappa statistics were calculated. Based on post-treatment OCT findings only (RR1), mean reinjection rate of all observers was 37.5%. Adding supplementary information, mean reinjection rate decreased to 20% when all information was available reflecting the 'real' situation (RR 6). Interobserver agreement rates varied from 66.7% to 90.7% depending on rating rounds and interobserver pairs. Mean AR and Kappa values (KV) were as following: AR 81.6%, KV 0.61 (RR1: 'only post-OP OCT'); AR 76.7%, KV 0.33 (RR2: post-OP OCT + SE); AR 80.3%, KV 0.45 (RR3: post-OP OCT + BCVA); AR 80.7%, KV 0.46 (RR4: pre- and post-OP OCT); AR 82.2%, KV 0.49 (RR5: post-OP OCT + SE + BCVA); and finally AR 83.6%, KV 0.47 (RR6: pre- and post-OP OCT + SE + BCVA). The overall mean agreement rate was 80.9% with a Kappa of 0.47. IOV for indicating retreatment after three Ranibizumab loading doses reveals only moderate agreement in Kappa statistics, which seems to be too low considering the high costs for retreatments. More concise guidelines based on the post-treatment OCT scans as the presumably most sensitive and noninvasive objective tool to follow choroidal neovascularization activity by judging the course of sub- and intraretinal fluid are necessary.

To investigate the effectiveness of repeated injections of intravitreal triamcinolone acetonide (IVTA) in the treatment of macular oedema caused by central retinal vein occlusion (CRVO). Seventeen pseudophakic or aphakic eyes of 17 patients (10 male, seven female) with macular oedema caused by CRVO received a repeat injection of 4 mg IVTA, 16 weeks after the first injection of the same dose. The examination included measurements of best-corrected visual acuity (BCVA) for distance and central foveal thickness (CFT) by optical coherence tomography (OCT), preoperatively and 1, 2, 3 and 4 months postoperatively. The values were compared by paired-t test. Side-effects were monitored. BCVA and CFT were not significantly different before initial and repeat injections. Transient improvements of BCVA and CFT were achieved after both injections. At the end of follow-up, BCVA and CFT were significantly different compared to pre-injection values in the same group (P = 0.032, 0.049 in the initial-injection group and P = 0.001, 0.008 in the repeat-injection group, respectively). However, compared to the initial injection, BCVA measurements were significantly worse at each time-point (P = 0.043, 0.011, 0.010 and 0.012, respectively) after the repeat injection, as were CFT at 1, 2 and 3 months post-injection (P = 0.040, 0.015 and 0.025, respectively). The achieved maximum mean intraocular pressures were 20.00 [standard deviation (SD) 2.06] mmHg and 18.56 (SD 3.65) mmHg after the first and repeat injections, respectively. These values were not significantly different (P = 0.467). No other significant adverse events were noted during the study. A repeat injection of 4 mg IVTA may not be as effective as an initial injection for the treatment of macular oedema caused by CRVO.

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

To describe different patterns of diabetic macular oedema (DMO) using a computerized alignment and averaging of sequences in optical coherence tomography (OCT) B-scans and to show the correlation of these patterns with the pathophysiology of the condition. We carried out a prospective, uncontrolled study, including 46 human subjects with untreated DMO. Enhanced OCT images were produced. We correlated different OCT patterns of DMO with ETDRS visual acuity and with the thickness of the central 1-mm of the macula. We also correlated these patterns with theories of the pathophysiology of DMO. Enhanced OCT images enabled us to examine how different layers of the macula were affected. The external limiting membrane (ELM) was clearly seen in all stages, including advanced stages. The sequence of DMO events in different macular layers can be divided into five patterns. Morphologically, DMO starts at the outer nuclear layer/Henle's layer. As the oedema progresses, cysts are seen in the fovea and the DMO spreads further into the inner nuclear layer. The ELM seems to act as a barrier for proteins and plays an important role in the development of DMO. Enhanced OCT revealed new details of DMO pathophysiology. The different morphological patterns of DMO seen in enhanced OCT may represent different levels of severity of the disease.

To investigate the incidence and cause of severe visual loss following use and removal of intraocular silicone oil (SiO) after uncomplicated vitrectomy and SiO injection for primary rhegmatogenous retinal detachment (RRD). Consecutive case series of 216 patients operated with vitrectomy for primary RRD in 2004-2005. In 162 eyes, SiO (5500 centiStoke) had been used as intravitreal tamponade and in 54 eyes gas (perflouropropane, C(3) F(8) ) had been used. Following chart review, we identified 16 eyes in 16 patients (nine SiO eyes, seven gas eyes) with macula-on and documented visual acuity ≥6/12 before surgery, where SiO had been removed, cataract surgery performed and no re-detachment had occurred. Examinations included best-corrected visual acuity (BCVA) and high-definition optical coherence tomography (OCT) of the macular area. Preoperative characteristics were identical between SiO and gas eyes. Postoperative BCVA was significantly worse in SiO eyes (>6/24) compared to gas eyes (>6/7.5), p = 0.005. Three of 9 (33%) SiO eyes had final BCVA ≤6/60 and 67% had final BCVA ≤6/12. No gas eyes had final BCVA <6/9. Macular OCT revealed thinning of inner retinal layers in SiO-operated eyes (5148 pixels) compared to gas-operated eyes (6897 pixels), p < 0.002. No other visually significant structural differences were found. Severe visual loss after SiO use was observed in 1/3 of patients with otherwise good visual potential. The visual loss was associated with a significant reduction in inner retinal thickness indicating neuronal cell loss in the macular area as a possible explanation.

Choroideremia Gene Therapy

To report the surgical outcome of pars plana vitrectomy (PPV) without internal limiting membrane (ILM) peeling in three highly myopic patients with macular retinoschisis and associated posterior staphyloma. We report three highly myopic patients with macular retinoschisis and foveal detachment who underwent simple PPV without ILM peeling, with long-acting gas tamponade. Main outcome evaluations included best corrected visual acuity, biomicroscopic appearance and optical coherence tomography findings. Pars plana vitrectomy without ILM peeling resulted in anatomic and functional improvement in all three operated eyes for follow-up periods of > or = 12 months. Pars plana vitrectomy without ILM peeling is effective for treating macular retinoschisis and foveal detachment in highly myopic eyes with posterior staphyloma. Visual and anatomic outcomes are comparable with those in previous studies in which ILM removal was performed.

Objective To observe the efficacy of vitrectomy combined with internal limiting membrane (ILM) peeling and scleral shortening for myopic foveoschisis (MF). Methods Prospective and non-randomized concurrent control study. A total of 35 MF patients (35 eyes) were enrolled in this study. The patients were divided into 2 groups according to surgery, including group A (18 eyes) and group B (17 eyes), all received vitrectomy combined with ILM peeling, but group A also received scleral shortening. The best corrective visual acuity (BCVA) examination using the Snellen vision chart was converted to the minimum resolution logarithm (logMAR). Ocular axis length (AL) was measured by Zeiss IOL-Master or A-scan ultrasound (Quantel Medical, France). The maximal value of retinal foveoschisis (MxFT) was measured by frequency-domain optical coherence tomography (Heidelberg, Germany). Multifocal electroretinogram (mfERG) responses were obtained with the RETIscan system (Roland Consult, Gemany).There was no statistically significant difference between the two groups (P>0.05) in age (t=0.460), AL (t=1.520), diopter (t=0.020), logMAR BCVA (t=−2.280), MxFT(Z=−4.179) and b-wave ERG amplitude (Z=−0.198). The changes of BCVA, AL, MxFT and b wave amplitude were followed-up for 3-12 months. Results At the last follow-up, the height of MF was decreased in 18 eyes of group A, and MF was completely disappeared in 4 eyes. The logMAR BCVA (t=7.272, 5.951), MxFT (Z=−3.724, −3.622) and b- wave ERG amplitude (Z=−3.223, −3.243) in both groups A and B were statistically improved (P=0.000, 0.000, 0.000, 0.000, 0.001, 0.001) compared to pre-operational results. There was significant difference of logMAR BCVA (t=−2.280) and MxFT (Z=−4.179) between the two groups (P=0.029, 0.000). But there was no significant difference in the amplitude of b-wave (Z=−0.198, P=0.843). The AL in group A was shortened after surgery, the difference was statistically significant (t=10.017, P=0.000). During the follow-up, there was no ocular hemorrhage, endophthalmitis and other complications. Conclusion PPV combined with ILM peeling and scleral shortening can shorten AL significantly for MF patients, and gain relative normal anatomical structure of the fovea, thus improve the vision. Key words: Myopia, degenerative/complications; Myopia, degenerative/surgery; Retinal perforations/surgery; Vitreoretinal surgery; Scleroplasty

Macular oedema is a common complication and vision-limiting factor in uveitis. The aim of this study was to compare retinal thickness as measured by optical coherence tomography and photoreceptor function as measured by fundus-related microperimetry with respect to their correlation with visual acuity. Prospective observational monocentre study. Thirty-one patients (53 eyes) with endogenous uveitis and fluorescein angiographically confirmed macular oedema were evaluated. Foveal thickness was analysed using spectral-domain (Spectralis(TM) ; Heidelberg Engineering, Heidelberg, Germany) OCT and retinal sensitivity was assessed using fundus-related microperimetry (MP1; Nidek Technologies, Padova, Italy). All findings were correlated with best-corrected visual acuity (BCVA). Foveal thickness was correlated with BCVA [p = 0.005, r = 0.38, 95% confidence interval (CI) 0.12-0.59]. For microperimetry measurements, a negative correlation with logMAR visual acuity was found. Fixation abnormalities were not associated with poor visual acuity, increased foveal thickness or retinal sensitivity. In eyes with cystoid changes in the outer plexiform and inner nuclear layer, foveal thickness was increased (p < 0.0001). Epiretinal membrane formation was present in 70%. In these eyes, foveal thickness was significantly increased (p = 0.003) and visual acuity was worse (p = 0.08). Foveal thickness and fundus-related microperimetry were correlated with visual acuity. Cystoid changes in the outer plexiform and inner nuclear layer and the presence of epiretinal membrane were associated with poor visual acuity. Fixation abnormalities were not associated with poor visual acuity.

En face optical coherence tomography for diagnosis of unexplained snowflake scotoma

To describe visual function and ocular manifestations in patients with onset of cholestasis during the neonatal period. Patients with neonatal cholestasis, either transitory or chronic, who came for assessment to our tertiary referral centre were included in a cross-sectional study and underwent ophthalmological examinations including fundus photography. A total of 57 patients (24 girls and 33 boys), aged 0.4-18.0 years, were included. Of these, 28 patients had biliary atresia, 11 had Alagille's syndrome, five had progressive familiar intrahepatic cholestasis and nine had different disorders such as pituitary insufficiency, alpha-1-antitrypsin deficiency, mitochondriopathy, congenital infections or cholestasis caused by unknown reasons. Visual dysfunction and/or one or several ocular manifestations occurred in 39 out of 57 patients. Major ocular malformations occurred in five patients. Out of three patients with biliary atresia, one patient had severe visual impairment caused by microphthalmia and chorioretinal coloboma, one patient with Cat Eye syndrome had bilateral uveochorioretinal coloboma and one patient had Rieger's anomaly. Two patients, both with pituitary deficiency and transient cholestasis, had severe unilateral visual impairment caused by optic nerve hypoplasia. The majority (68%) of the patients with cholestasis had ocular manifestations. Although the severity of ocular complications varied with diagnosis, and was most apparent among patients with biliary atresia or pituitary deficiency, no conclusion can be drawn regarding the connections between these conditions from the present study. Nevertheless, ocular assessment is important for diagnostic purposes and for early intervention in patients with cholestasis.

Benign yellow-dot maculopathy: case report and review of the literature

Objective To observe the clinical features, phenotypes and genotypes in a Chinese family with choroideremia (CHM). Methods A Chinese four-generation family (15 members) with CHM, including 5 patients (4 males/1 female), 2 female carriers and 8 healthy members, was enrolled in this study. Initially all family members underwent best corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus fluorescein angiography, optical coherence tomography (OCT), visual field and full view electroretinogram (ERG). BCVA was followed up for 3 years. Venous blood samples were collected, and all of the 15 coding exons and flanking intron regions were amplified in the proband by polymerase chain reaction followed by direct sequencing. Protein structure was modeled based on the protein data bank and mutations in DeepView v4.0.1 to predict the effect of the mutations. A total of 180 healthy volunteers were enrolled as control group to matching CHM gene sequences. Results The visual acuity (VA) of 3/4 adult male patients began to decrease at less than 10, 10 and 30 years old, the average BCVA was 0.43. There were characteristic signs and symptoms of CHM including narrow visual field, extinguished rod and cone response in ERG, disappeared junction line and intermediate line of photoreceptor inner segment/outer segment on OCT. After 3 years, the mean BCVA decreased to 0.11. The BCVA of one young male patient was 1.0 in both eyes with minor changes fundus and visual field. The VA of the female patient began to decrease at 50 years old, her BCVA of two eyes were 0.5 and 0.25, respectively. The fundus changes were typical of CHM, with relative scotomas in the peripheral visual field of OD, and big scotomas in the OS. After 3 years, her mean BCVA decreased to 0.2. Of 2 female carriers, one had minor fundus changes (patches of pigmentary deposits, atrophy spots of retinal pigment epithelium cells), and the other was normal. A novel heterozygous c.1837G> A mutation in exon 15 of CHM was detected in the proband, which resulted in the substitution of serine by proline at codon 613 (p.D613N). Based on molecular modeling, the misfolded protein caused by the mutation might destabilize the structure of the helix that potentially could affect the global stability of the Rep-1 protein. Conclusions A novel c.1837G> A (p.D613N) mutation may be the causative mutation for CHM in this family. Female CHM carriers may have some signs and symptoms. Key words: Choroid diseases/diagnosis; Eye diseases, hereditary; DNA mutational analysis