Photoreceptor inner and outer segment layer thickness in multiple evanescent white dot syndrome

Purpose

To evaluate the photoreceptor inner and outer segment layer thickness in eyes with MEWDS.

Design

Prospective, non-comparative, observational case series. The follow-up duration was 4 months.

Methods

Four women were diagnosed with unilateral MEWDS. The ages of the patients were 25, 24, 35, and 40 years. The retinal microstructure was assessed by spectral-domain optical coherence tomography (SD-OCT). The thickness of the photoreceptor inner (IS) and outer (OS) segments and sum of them (IS + OS) at the fovea were analyzed.

Results

The visual acuity was reduced in three of four eyes at the acute phase. SD-OCT showed that the border of IS and OS (IS/OS) line and the cone outer segment tips (COST) line in the macula area were not detected in all four eyes. The IS + OS thickness was 50.3?±?5.6 μm and that of the healthy fellow eyes was 73.5?±?7.0 μm (n?=?4 eyes). The thickness of the IS was 27.8?±?2.6 μm and that of the OS was 45.8?±?7.3 μm. In all eyes, there was a spontaneous improvement of the visual acuity. SD-OCT showed a recovery of only the IS/OS line in the macular area, but the COST line was not visible in three cases. The mean IS + OS thickness increased to 56.0?±?7.9 μm (n?=?4), IS?=?26.0?±?2.0 μm (n?=?3), and OS?=?30.1?±?8.7 μm (n?=?3) in the early recovery phase, and to 64.8?±?9.3 μm (n?=?4), IS?=?28.5?±?1.7 μm (n?=?4), and OS?=?36.3?±?7.9 μm (n?=?4) in the late recovery phase. The mean inner and outer segment thickness remained unchanged in the fellow eyes.

Conclusion

Eyes with MEWDS have changes in the photoreceptor microstructures. The change in the IS + OS thickness during the natural recovery course might be due to an increase in the OS length.     

Tocilizumab treatment for refractory uveitis-related cystoid macular edema

Background

This retrospective study investigated the efficacy of tocilizumab (TCZ), a fully humanized antibody that binds both to soluble and membrane bound IL-6 receptors, for the treatment of uveitis-related cystoid macular edema (CME) refractory to immunomodulatory therapy.

Methods

Five refractory patients with uveitis-related CME who received TCZ between January and August 2012 were included. All patients received 8 mg/kg TCZ at 4-week intervals. Data regarding patient demographics, use of immunosuppressive drugs, biologic agents or intravitreal therapies prior to TCZ infusions were collected. Main outcome measure was central foveal thickness (CFT) measured by optical coherence tomography at 6 months. Secondary outcome measures were degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria) and visual acuity (logarithm of the minimum angle of resolution [log-MAR]) at month 6. Adverse events (AEs) related to TCZ therapy were also assessed.

Results

Eight eyes from five patients (all females) were included. Mean age was 49.4 years (range, 30–68). Mean follow-up was 8.4 months (range, 6–12). Before TCZ, all patients received and failed conventional immunosuppressive therapy and had received at least another biologic agent. Uveitis diagnoses were Birdshot chorioretinopathy (n?=?3), juvenile idiopathic arthritis (JIA)-associated uveitis (n?=?1), and idiopathic panuveitis (n?=?1). Mean evolution of CME was 13.4 years (range, 2–30). Mean baseline CFT (95 % confidence interval) was 602?±?236 μm at baseline, 386?±?113 μm at month 1 (p?=?0.006), 323?±?103 μm at month 3 (p?=?0.026), and 294.5?±?94.5 μm at month 6 (p?=?0.014). Median best-corrected visual acuity (BCVA) improved from 0.66?±?0.57 at baseline to 0.47?±?0.62 at month 6 (p?=?0.035). After 6 months, an improvement of ≥ 2 lines of BCVA was observed in 50 % of eyes (p?=?0.028) remained stable in 25 % and worsened in none of the patients. Sustained uveitis remission was achieved in all patients. No AEs were reported.

Conclusions

These data suggest that TCZ is effective for treating CME in otherwise treatment-refractory cases of uveitis.     

The effect of photodynamic therapy on macular sensitivity in eyes with acute central serous chorioretinopathy

Background

To evaluate the effect of half-fluence rate indocyanine green angiography (ICGA)-guided verteporfin photodynamic therapy (PDT) on macular sensitivity (MS) in eyes with acute symptomatic central serous chorioretinopathy (CSC).

Methods

Single-center consecutive case series by retrospective chart review. Sixteen eyes of 16 patients with acute CSC of 3 months duration or less, treated with half-fluence (25 mJ/cm²) ICGA-guided verteporfin PDT were reviewed. At baseline and after 1, 3, and 6 months, all patients underwent MS testing of the central 20 °, MS testing of the retinal area covered by the PDT laser spot (MSLS), and evaluation of fixation stability (FS) for the central two degrees with the MP-1 microperimeter (Nidek, Vigonza, Italy).

Results

Macular sensitivity improved from 16.4?±?3.0 dB at baseline (n?=?16) to 18.2?±?2.4 dB (p?<?0.001) at 1 month (n?=?16). At the 3-month (n?=?13) and 6-month (n?=?12) follow-up, MS stabilized at 19.5?±?0.9 dB (p?=?0.21) and 19.0?±?1.3 dB (p?=?0.74), without changes when compared to respective precedent follow-up. Mean MSLS improved from 12.9?±?5.4 dB at baseline to 16.4?±?4.9 dB (p?<?0.001) after 1 month. At the 3- and 6-month follow-up, MSLS was 19.1?±?1.2 dB (p?=?0.1) and 18.9?±?1.9 dB (p?=?0.8) respectively. Mean FS at the central 2 ° was 78.8?±?30.4 % before treatment and 81.8?±?29.5 % (p?=?0.7), 81.9?±?27.5 % (p?=?0.7) and 83.6?±?17.1 % (p?=?0.5) respectively 1, 3 and 6 months after treatment.

Conclusion

Half-fluence (25 mJ/cm²) PDT significantly increased mean MS of central 20 ° and mean MSLS, in eyes with acute symptomatic CSC. Fixation stability was stable at baseline and throughout 6 months of follow-up.     

Comparison of Spectralis-OCT, GDxVCC and GDxECC in assessing retinal nerve fiber layer (RNFL) in glaucomatous patients

Background

Glaucomatous optic neuropathy is characterized by a progressive loss of retinal ganglion cells (RGCs). The defects in the peripapillary retinal nerve fiber layer (RNFL) have been reported to be the earliest sign of glaucoma. We determined the agreement between RNFL thickness assessments from spectral-domain OCT (Spectarlis HRA?+?OCT; Heidelberg Engeneering, Heidelberg, Germany), scanning laser polarimetry (SLP) with variable cornea compensation (GDxVCC; Carl Zeiss Meditec, Dublin, CA, USA), and SLP with enhanced cornea compensation (GDxECC; Carl Zeiss Meditec, Dublin, CA, USA) in glaucomatous patients. Furthermore, we investigate the influence of typical scan score (TSS) on the results of GDx assessments.

Methods

The enrolled subjects were devided into different groups by modified HODAPP visual field criteria. The peripapillary RNFL thickness was assessed with the three devices . ANOVA test, Pearson and Spearman correlation coefficient, and Bland-Altman plots were used to analyse the RNFL thickness assessments.

Results

Ninety-two eyes from 92 glaucomatous subjects were analysed. These were divided into four groups: preperimetric glaucoma (n?=?26), mild glaucoma (n?=?18), moderate glaucoma (n?=?21), and severe glaucoma (n?=?27). For Spectralis-OCT, the average RNFL thickness (mean ± SD) was 99.25?±?26.31 μm, 80.52?±?16.63 μm, 71.59?±?21.15 μm, and 63.85?±?20.86 μm for preperimetric, mild, moderate, and severe glaucoma respectively. For GDxVCC, the corresponding assessments were 52.63?±?8.18 μm, 52.95?±?10.20 μm, 46.77?±?10.62 μm, and 49.70?±?13.34 μm. For GDxECC, the assessments were 49.35?±?6.52 μm, 45.92?±?7.21 μm, 42.19?±?8.00 μm, and 39.53?±?8.45 μm. All Spectralis-GDxVCC and Spectralis-GDxECC differences were statistically significant by ANOVA test. The differences between GDxVCC and GDxECC were statistically significant only for severe glaucoma. There was a highly significant correlation between Spectralis-OCT and GDxECC, as well as Spectralis-OCT and GDxVCC, in assessing the RNFL thickness. The best instrument agreement was found between GDxECC and Spectralis-OCT. The RNFL thickness assessed with Spectralis-OCT and GDxECC showed a better correlation to visual field defects than GDxVCC. Evaluating GDx assessments with typical retardation pattern GDxVCC and GDxECC showed very similar RNFL thickness results.

Conclusions

RNFL thickness assessments between GDxVCC, GDxECC, and Spectralis-OCT cannot be directly compared. The assessments are generally higher with Spectralis-OCT than with GDxVCC and GDxECC, because of differences in method of the devices. The atypical retardation pattern has a major impact on the RNFL thickness results of GDx devices. This must be taken into account when evaluating the assessed RNFL thickness results.     

Everolimus for the treatment of uveitis refractory to cyclosporine A: a pilot study

Background

This study investigated the efficacy of everolimus, a potent inhibitor of T lymphocyte proliferation, for treating noninfectious uveitis. The study design was an open-label prospective trial.

Methods

Twelve patients with severe chronic uveitis (anterior and intermediate n?=?9, panuveitis n?=?3) refractive to cyclosporine A (CsA) received additional everolimus. Main outcome measure: the primary outcome measure was uveitis inactivity at 3 months. Secondary outcome measures were uveitis recurrence, visual acuity (BCVA), laser flare photometry values, cystoid macular edema, and tapering of concomitant corticosteroids and/or immunosuppressive drugs in 12 months with the addition of everolimus and after withdrawing everolimus. Percentages of peripheral blood CD3⁺CD4⁺CD25⁺Foxp3⁺ cells were studied.

Results

At month 3 with everolimus, uveitis was inactive in all patients. By 12 months, uveitis had recurred in four patients after tapering (n?=?2) or withdrawing (n?=?2) CsA. BCVA remained stable in all patients, mean foveal thickness (OCT) was slightly reduced from 308 μm at baseline to 255 μm (p?=?0.1), and mean flare values were slightly reduced from 27.8 to 19.3 photons/msec (p?=?0.1). It was possible to achieve a 50 % dose reduction of systemic prednisone (n?=?8) or CsA (n?=?8). After withdrawing everolimus, uveitis recurred in 50 % within 1 month; by 6 months, BCVA dropped ≥2 lines in five patients, and prednisone use increased ≥50 % in four patients. The percentage of peripheral blood CD3⁺CD4⁺CD25⁺FoxP3⁺ T cells increased during the everolimus treatment, and dropped after withdrawal.

Conclusions

Uveitis inactivity was achieved with the addition of everolimus in patients with chronic, CsA-refractive anterior and intermediate uveitis, or panuveitis.     

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration

Background

Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities.

Methods

Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected.

Results

After an initial increase to a value of +5.0?±?11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of ?0.66?±?16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1?±?191.4 μm at baseline to a value of 289.9?±?138.6 μm after initial therapy and stabilized at a value of 322.4?±?199.5 μm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (?2.2?±?5.0 versus 0.4?±?7.4 letters; p?=?0.046).

Conclusions

Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.     

Retinal and optic nerve evaluation by optical coherence tomography in adults with obstructive sleep apnea–hypopnea syndrome (OSAHS)

Objective

To assess the peripapillary retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) morphologic parameters, and macular thickness and volume in patients affected by obstructive sleep apnea–hypopnea syndrome (OSAHS).

Methods

This prospective, observational case-control study consisted of 96 eyes of 50 OSAHS patients (mean age of 50.9?±?12.4 years, best-corrected visual acuity ≥20/20, refractive error less than 3 spherocylindrical diopters, and intraocular pressure <21 mmHg) who were enrolled and compared with 64 eyes of 33 age-matched controls. Peripapillary RNFL thickness, ONH parameters, macular thickness and volume were measured by optical coherence tomography (OCT).

Results

OSAHS patients showed a significant reduction of the nasal quadrant RNFL thickness (74.7?±?15.8 μm) compared with those values observed in control patients (81.1?±?16.6 μm, p?=?0.047, Student's t-test). No differences in peripapillary RNFL thickness were observed when dividing the OSAHS group in accordance with disease severity. Vertical integrated rim area (VIRA) (0.67?±?0.41 mm³ in OSAHS vs 0.55?±?0.29 mm³ in controls; p?=?0.043, Student's t-test), horizontal integrated rim width (HIRW) (1.87?±?0.31 mm² in OSAHS vs 1.8?±?0.25 mm² in controls; p?=?0.039, Student's t-test) and disc area (2.74?±?0.62 mm² in OSAHS vs 2.48?±?0.42 mm² in controls; p?=?0.002, Student's t-test) showed significant differences, all of them being higher in the OSAHS group. Severe OSAHS had significant higher disc area (2.8?±?0.7 mm²) than controls (2.5?±?0.4 mm²; p?=?0.016, ANOVA test). Temporal inner macular thickness was significantly higher in mild–moderate OSAHS patients (270?±?12 μm) than in severe OSAHS patients (260?±?19 μm; p?=?0.021, ANOVA test).

Conclusions

OSAHS patients showed decreased peripapillary nasal RNFL thickness, and increased ONH area and volume parameters when they were evaluated by OCT. These findings suggest that neuronal degeneration might be present in the retina of OSAHS patients, as previously observed in some neurodegenerative disorders     

Clinical features of IgG4-related dacryoadenitis

Background

To elucidate the clinical characteristics of IgG4-related dacryoadenitis.

Methods

Clinical features, laboratory findings, radiological findings, associated diseases, treatment, and prognosis were prospectively examined in 12 patients (seven men, five women; mean age, 60.9?±?15.1 years) with IgG4-related dacryoadenitis.

Results

In addition to eyelid swelling, other ophthalmologic symptoms were observed in seven patients, including diplopia (n?=?4), ptosis (n?=?2), visual field disturbance (n?=?2), eye pain (n?=?2), decrease of visual acuity (n?=?2), eye-movement disturbance (n?=?1), dry eye (n?=?1), corneal ulcer (n?=?1), and epiphora (n?=?1). Swelling of the lacrimal glands was bilateral in half of the patients. Other IgG4-related diseases were present in nine patients, including sialadenitis (n?=?5), autoimmune pancreatitis (n?=?4), retroperitoneal fibrosis (n?=?2), and lymphadenopathy (n?=?8). Serum IgG4 levels were significantly higher in patients with other IgG4-related disease (1070?±?813 mg/dl) than in those without (197?±?59 mg/dl, p?=?0.017). Allergic histories and elevated serum IgE levels were each detected in six patients. Eight patients showed inflammatory extension beyond the lacrimal gland, such as thickened rectus muscle (n?=?6), inflammation of the optic nerve (n?=?2), and retrobulbar inflammation (n?=?3). Steroid therapy was effective in seven patients, but dacryoadenitis relapsed in two patients with markedly higher serum IgG4 levels and autoimmune pancreatitis.

Conclusions

IgG4-related dacryoadenitis showed various ophthalmologic symptoms due to extensive inflammation beyond the lacrimal gland, frequent association with other IgG4-related disease or allergic phenomena, and steroid responsiveness.     

Response to anti-VEGF therapy in patients with subretinal fluid and pigment epithelial detachment on spectral-domain optical coherence tomography

Purpose

To analyse the long-term functional and morphological response of a specific choroidal neovascular membrane (CNV) phenotype to anti-vascular endothelial growth factor (VEGF) therapy.

Methods

Data from 30 eyes of 30 consecutive patients with subretinal fluid (SRF) and fibrovascular pigment epithelial detachment (PED) due to CNV on spectral-domain optical coherence tomography (SDOCT) with a follow-up of at least 20 months were retrospectively collected. Main outcome measures included change in visual acuity, quantitative and qualitative parameters on SDOCT [photoreceptor layer, outer nuclear layer (ONL), choroid, PED, SRF] and on fluorescein angiography (CNV activity). Subjects were divided into responders and non-responders based on morphological and functional aspects.

Results

An average number of 20.23?±?9.9 anti-VEGF injections were administered during a mean follow-up of 40.25?±?13.5 months. Fourteen eyes were categorized as morphological non-responders, 12 as functional non-responders and eight as complete non-responders. Complete non-responders were significantly younger than complete responders (68.5?±?4.5 vs 74.3?±?6.8 years; p?<?0.05) and presented thinner baseline ONL values (68.43?±?15.2 vs103.5?±?32.8 μm; p?<?0.05). Intermediate or large drusen as typical features for age-related macular degeneration (AMD) were less frequently present in complete non-responders; however, this was not statistically significant (62.5 % vs 91.7 %; p?=?0.25).

Conclusions

Our preliminary findings indicate that eyes with the specific SDOCT phenotype with isolated fibrovascular PED and SRF frequently demonstrate non-response to anti-VEGF therapy, and the underlying disease mechanism may be different from AMD. Larger prospective trials are required to validate those results, and to develop strategies to improve the morphological as well as functional outcome.     

Comparison of dynamic contour tonometry and Goldmann applanation tonometry in relation to central corneal thickness in primary congenital glaucoma

Background

To compare intraocular pressure (IOP) measurements obtained with dynamic contour tonometer (DCT) and Goldmann applanation tonometer (GAT), and to investigate their relationship to central corneal thickness (CCT) in primary congenital glaucoma (PCG) eyes.

Methods

Thirty-one eyes of 31 PCG patients (25.7?±?7.2 years old) were examined. PCG was defined as elevated IOP, enlarged corneal diameter (buphthalmos), Haab’s striae and abnormal findings at gonioscopy. The mean of three measurements of GAT, DCT (quality scores 1 and 2), and CCT were obtained and assessed for agreement by means of Bland–Altman plot and for Spearman correlation test.

Results

Mean CCT was 534?±?72.3 μm (range: 430 to 610 μm). Mean IOP measurements were 15.1?±?4.2 mmHg (range: 5.5 to 22.7 mmHg) for DCT and 14.5?±?5.6 mmHg (range: 7.0 to 34.0 mmHg) for GAT (P?=?0.244). Spearman correlation tests showed that IOP difference (DCT ? GAT) was not correlated with CCT (r ²?=?0.023, P?=?0.417). IOP measurements by DCT were weakly but statistically correlated with those obtained with GAT (r²?=?0.213, P?=?0.0089). Bland–Altman analysis revealed poor agreement between DCT and GAT readings, considering the 95 % confidence intervals of ±10.45 mmHg.

Conclusions

The differences between DCT and GAT readings were not influenced by CCT in this series of patients. Considering the weak correlation and the poor agreement observed between GAT and DCT measurements and that they both may be affected by corneal biomechanical changes, these methods should not be used interchangeably, and may possibly give no meaningful IOP values in PCG patients.     

Pain score of patients undergoing single spot, short pulse laser versus conventional laser for diabetic retinopathy

Background

To compare pain score of single spot short duration time (20 milliseconds) panretinal photocoagulation (PRP) with conventional (100 milliseconds) PRP in diabetic retinopathy.

Methods

Sixty-six eyes from 33 patients with symmetrical severe non-proliferative diabetic retinopathy (non-PDR) or proliferative diabetic retinopathy (PDR) were enrolled in this prospective randomized controlled trial. One eye of each patient was randomized to undergo conventional and the other eye to undergo short time PRP. Spot size of 200 μm was used in both laser types, and energy was adjusted to achieve moderate burn on the retina. Patients were asked to mark the level of pain felt during the PRP session for each eye on the visual analog scale (VAS) and were examined at 1 week, and at 1, 2, 4 and 6 months.

Results

Sixteen women and 17 men with mean age 58.9?±?7.8 years were evaluated. The conventional method required a mean power of 273?±?107 mW, whereas the short duration method needed 721?±?406 mW (P?=?0.001). An average of 1,218?±?441 spots were delivered with the conventional method and an average of 2,125?±?503 spots were required with the short duration method (P?=?0.001). Average pain score was 7.5?±?1.14 in conventional group and 1.75?±?0.87 in the short duration group (P?=?0.001). At 1 week, 1 month, and 4 months following PRP, the mean changes of central macular thickness (CMT) from baseline in the conventional group remained 29.2 μm (P?=?0.008), 40.0 μm (P?=?0.001), and 40.2 μm (P?=?0.007) greater than the changes in CMT for short time group.

Conclusion

Patient acceptance of short time single spot PRP was high, and well-tolerated in a single session by all patients. Moreover, this method is significantly less painful than but just as effective as conventional laser during 6 months of follow-up. The CMT change was more following conventional laser than short time laser.     

Macular pigment optical density measurements by one-wavelength reflection photometry—influence of cataract surgery on the measurement results

Purpose

The main objective of the present study was the investigation of possible influence of lens opacification on macular pigment optical density (MPOD) measurements.

Methods

Eighty-six eyes of 64 patients (mean age 73.4 ± 8.3 years) were included in the study. MPOD was prospectively measured using the one-wavelength reflection method (Visucam500, Carl Zeiss Meditec AG) before and after cataract extraction, with implantation of a blue-light filtering intraocular lens (AlconSN60WF). The median of the maximum optical density (MaxOD) and the median of the mean optical density (MeanOD) measurements of macular pigment across the subject group were evaluated.

Results

Statistically significant differences were noticed between pre-operative and post-operative measurements, the absolute values were generally lower after cataract extraction. The following median (lower/upper quartile) differences across the group were determined: MaxOD ?33.8 % (?46.2 to ?19.1 %), MeanOD ?44.0 % (?54.6 to ?26.6 %). Larger changes were observed in elderly patients [<70 years of age (n?=?25 eyes): MaxOD ?13.4 % (?20.5 to 3.6 %), MeanOD ?23.6 % (?30.5 to ?15.3 %) versus patients ≥70 years (n?=?61 eyes) MaxOD ?40.5 % (?53.2 to ?30.1 %), MeanOD ?47.2 % (?57.8 to ?40.1 %)] and in patients with progressed stage of cataract. MaxOD for lens opacification grade 1 (n?=?9 eyes): ?27.4 % (?42.1 to ?19.6 %), grade 2 (n?=?26 eyes): ?35.0 % (?44.2 to ?25.3 %), grade 3 (n?=?21 eyes): ?34.4 % (?45.4 to ?11.4 %), grade 4 (n?=?25 eyes): ?32.6 % (?53.2 to ?6.4 %), and grade 5 (n?=?5 eyes): ?53.5 % (?61.7 to ?38.7 %) and MeanOD for cataract stage 1 (n?=?9 eyes): ?42.6 % (?46.0 to ?26.0 %), stage 2 (n?=?26 eyes): ?44.1 % (?51.8 to ?26.2 %), stage 3 (n?=?21 eyes): ?45.7 % (?54.7 to ?24.7 %), stage 4 (n?=?25 eyes): ?39.5 % (?59.4 to ?26.1 %), and stage 5 (n?=?5 eyes): ?57.0 % (?66.1 to ?51.4 %).

Conclusions

As established by comparison of pre- to post-operative measurements, cataract presented a strong effect on MPOD measured by one-wavelength reflection method. Particular care should therefore be taken when evaluating MPOD using this method in elderly patients with progressed stage of cataract. Future optimization of correcting parameters of scattered light and consideration of cataract influence may allow more precise evaluation of MPOD.     

Morphometric analysis of postoperative corneal neovascularization after high-risk keratoplasty: herpetic versus non-herpetic disease

Background

Postoperative complications after high-risk corneal grafting are decisively associated with corneal neovascularization (CNV). This study aimed to identify the incidence, extent, speed, localization, and influence of surgery-related factors on CNV after high-risk penetrating keratoplasty (PK) and to evaluate the effect of removing the angiogenic stimulus, i.e., residual components of herpes simplex virus (HSV) on postkeratoplasty CNV in patients with herpetic stromal keratitis (HSK).

Methods

All primary high-risk PK performed for HSK and non-herpetic keratitis (controls) between 1 January 1998 and 31 December 2003 at our department with available standardized corneal photographs taken preoperatively as well as 6?weeks, 3, 6 and 12?months postoperatively were evaluated (n _herpes?=?19, n _controls?=?5 patients). Maximal extension of CNV, limbus suture distance (LSD), limbus graft distance (LGD) and graft size in digitalized pictures were measured in each of the 16 sectors of the cornea at every visit.

Results

One hundred percent of the prevascularized corneas (n?=?24) showed further CNV outgrowth within 1?year after keratoplasty, while 58?% of these patients featured high-grade CNV reaching the host–graft junction or invading the donor tissue. Overall, CNV outgrowth was fastest during the first 6?weeks after PK, with a mean speed of 48?μm/week. Mean CNV growth speed within 6?months post-PK was significantly lower in the herpes group (13?μm/week) than in the non-herpes group (25?μm/week, p?=?0.017). Corneal location around the 12 o'clock position showed the most intense vessel outgrowth, which proved to be an independent risk factor for high-grade CNV (p?=?0.025). Inverse correlation was evident between CNV growth speed and LSD (p?=?0.032).

Conclusions

Additional intense CNV outgrowth is a common phenomenon after high-risk keratoplasty, strongly marked in the early postoperative period. The removal of residual HSV components representing a potential angiogenic stimulus leads to a reduction in corneal angiogenesis not in the short term, but in the long term after PK in patients with HSK. In addition to preferable atraumatic operation techniques, modern antiviral prophylaxis and anti-angiogenic therapy should be applied early, possibly even prior to transplantation. Short LSD seems to be an intraoperative adjustable risk factor for CNV in high-risk setting. Attention should also be paid to the superior site around the 12 o'clock position.     

Retinal vessel diameter in normal-tension glaucoma patients with asymmetric progression

Purpose

To investigate the longitudinal changes in the central retinal vessel diameter in asymmetric progressive normal-tension glaucoma (NTG) patients.

Methods

This study included 27 patients with bilateral NTG without any systemic vascular disease who showed glaucomatous progression in one eye at the mean follow-up of 24.3 months (range, 18–29 months). Progression was determined by the development of new retinal nerve fiber layer (RNFL) defects or widening of pre-existing defects on red-free RNFL photographs. The central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE) were measured at baseline and at the mean follow-up of 24.3 months. We classified the eyes of each patient as either progressed or stable eyes, and compared the differences and changes in the CRAE and CRVE.

Results

No significant inter-eye difference was observed at baseline in the mean CRAE (167.5?±?22.2 μm vs. 168.2?±?15.5 μm, p?=?0.809) and in the mean CRVE (276.3?±?18.2 μm vs. 281.6?±?21.9 μm, p?=?0.267) between the progressed and stable eyes. There were significant changes in CRAE in the progressed eyes between baseline and 2 years after baseline (from 167.5?±?22.2 μm to 146.9?±?18.0 μm, p?p?=?0.084).

Conclusions

In our series of NTG patients with asymmetric progression, central retinal artery diameter decreased over time in the progressed eyes, whereas no significant decrease in the central retinal artery diameter was seen in the stable eyes.     

Bimonthly injections of ranibizumab for age-related macular degeneration

Purpose

To evaluate the efficacy of bimonthly intravitreal injections of ranibizumab for age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in a pilot study.

Methods

This study was a prospective, interventional case series. Thirty eyes of 30 patients received prospectively at least three bimonthly intravitreal injections of ranibizumab (0.5 mg/0.05 ml) without loading doses. The best-corrected visual acuity (BCVA) and the central retinal subfield thickness (CRST) were measured before and monthly after the injections.

Results

Twenty-eight patients received the three planned injections; one patient refused the third injection, one patient did not receive the third injection because blood pressure was raised, and one patient received a rescue injection at month 5 because of increased retinal thickness. The mean logarithm of the minimum angle of resolution (logMAR) BCVA was 0.44?±?0.37 before treatment and significantly improved to 0.25?±?0.34 at month 6 (p?p?p?=?0.005). The mean CRST was 360?±?110.8 μm before treatment and decreased significantly to 249?±?57.0 μm at month 12 (p?=?0.025).

Conclusions

Bimonthly injections of ranibizumab may be effective for treating AMD and PCV.     

Comparison of spectral-domain and high-penetration OCT for observing morphologic changes in age-related macular degeneration and polypoidal choroidal vasculopathy

Background

We compared the visibility of retinal and choroidal pathologies using high-penetration optical coherence tomography (HP-OCT) with a long-wavelength light source (1,050 nm) and conventional spectral-domain OCT (SD-OCT) in age-related macular degeneration (AMD).

Methods

One hundred and forty-six eyes were included: 63 eyes with AMD, 79 eyes with polypoidal choroidal vasculopathy (PCV), and four eyes with retinal angiomatous proliferation. The SD-OCT and HP-OCT images were compared using the grading criteria to grade the visibility of the retinal changes, the line corresponding to the retinal pigment epithelium (RPE), and the chorioscleral interface (CSI). In 132 eyes with a pigment epithelial detachment (PED), we graded the structures inside the PED, Bruch’s line, and the CSI. We compared the visibility of those changes in eyes with subretinal hyperreflective changes due to a subretinal hemorrhage (SRH) (n?=?17) or a hemorrhage inside the PED (HPED) (n?=?12).

Results

HP-OCT provided superior visibility of the following structures compared to SD-OCT (P?<?0.01): the CSI, structures inside the PED, Bruch’s line inside the PED, the CSI inside the PED, SRH, type 1 CNV, polyps, and HPED. There were no significant differences between the two OCT devices in the scores for the RPE line, retinal morphology, or type 2 CNV and/or fibrin.

Conclusion

HP-OCT visualizes morphologies beneath the RPE better than SD-OCT, and is equivalent to SD-OCT for visualizing morphologies above the RPE.     

“OSMO-UT-DSAEK” using THIN-C medium

Background

When performing ultra-thin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK), the quality of the stromal interface and stromal thickness seem to be critical for visual outcome. The aim of this study was to investigate whether additional osmotic deswelling prior to UT-DSAEK improves the quality of the cut surface and leads to a more reliable and deeper cut in UT-DSAEK (“OSMO-UT-DSAEK”).

Methods

Seventeen human donor corneas not usable for transplantation were used in this experiment. After standard deswelling with culture Medium II, ten corneas were randomly assigned to be additionally deswollen within THIN-C medium. The other remaining seven corneas were put back into culture Medium II. All corneas were placed in an artificial anterior chamber system (Moria); a double path cutting procedure using a microkeratome (Moria) was then performed. Corneal thickness was measured by ultrasound biomicroscopy and in paraffin-embedded slides, followed by histological grading of the cut surface.

Results

Stromal interface smoothness significantly improved after preconditioning in THIN-C medium (Pearson P?=?0.019). The correlation of the corneal thickness obtained by UBM (mean 706?±?SD 208 μm) and histology (mean 530?±?SD 159 μm) was not significant (Pearson r?=?0.11, P?>?0.05, mean difference 247, 95 % CI [+50;+304]). We found no significant correlation between the microkeratome setting and the actual thickness of the lenticule measured in histological analysis in both media as well as for the first and second cut (first cut: Pearson r?=?0.9, P?=?0.1, 95 % CI [?10;+96], second cut: Pearson r?=?0.9, P?=?0.4, 95 % CI [?10;+22]).

Conclusion

Preconditioning of corneas with THIN-C medium significantly improved the quality of the graft interface in UT-DSAEK, but did not significantly improve the cut precision of the microkeratome.     

Comprehensive approach to ocular consequences of Stevens Johnson Syndrome - the aftermath of a systemic condition

Background

Stevens Johnson Syndrome (SJS) can lead to end stage corneal blindness. This study describes the comprehensive treatment measures and their outcomes in the management of ocular sequelae and complications of SJS.

Methods

Four hundred sixty-four eyes of 232 patients of SJS who underwent surgical intervention (punctal cautery, mucus membrane grafting for lid margin keratinisation, fornix reconstructive procedures, tectonic procedures, keratoplasty and keratoprosthesis) were studied. It was a non-comparative, retrospective, interventional case series. The primary outcome was the change in the best corrected visual acuity (BCVA). Secondary outcome measures included an improvement in the ocular surface status as indicated by corneal epithelial fluorescein staining and Schirmer’s I strip wetting.

Results

The BCVA and the ocular surface status improved and/or stabilized in?>?70 % of eyes following punctal cautery (n?=?160) and > 80 % of eyes following lid margin mucus membrane grafting (n?=?238). BCVA improved in 50 % of eyes following fornix reconstructive procedures (n?=?24) with COMET (n?=?6), in 63.9 % eyes with the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) lens (n?=?36), in 81.8 % of eyes after cataract surgery (n?=?22). A BCVA of ≥20/200 was achieved in 72.34 % of eyes following keratoprostheses procedures (n?=?47). The mean duration of follow up was 53.3?±?15.2 months.

Conclusion

The ocular sequelae of Stevens Johnson Syndrome can be blinding. They need to be identified and addressed early to retard the continued deterioration of the ocular surface. Our study aims to highlight the problem as well as the importance of comprehensive measures in the management of this potentially blinding disorder.     

Alternative route for erythropoietin ocular administration

Purpose

This study aimed to find an alternative route for erythropoietin (EPO) ocular administration because of its neuroprotective and neuroregenerative known properties. Ocular penetration of EPO after subconjunctival injection was assessed, and potential side-effects on the haematocrit for a 28-day period were also evaluated.

Methods

Wistar Hannover female albino rats (n?=?42) divided into seven groups of six were used. One group (n?=?6) served as control. Six groups (n?=?36) received 1,000 UI of EPO through the subconjunctival route in one of the eyes. According to the group, animals were humanely killed at 12 h (n?=?6), 24 h (n?=?6), 36 h (n?=?6), 48 h (n?=?6), and 60 h (n?=?6), after EPO administration, in a total of 30 animals. Enucleation of both eyes was performed, and EPO protein distribution in the rat’s retina was analyzed by immunohistochemistry. Another group of animals (n?=?6) was used to collect blood samples and perform haematocrit analysis at 0, 7, 14, 21, and 28 days after unilateral EPO subconjunctival administration.

Results

The evaluation of EPO expression in the animals' retinas after subconjunctival administration yielded a strong immunostaining signal. Among the retina’s layers, EPO expression was more evident in the RGC layer 24 h after the administration, and was still present on that layer till the end of the study (60 h). When administered subconjunctivally EPO reached several neuronal cells, in all retinal layers. The subconjunctival EPO administration did not cause significant changes in the haematocrit values over a 28-day period.

Conclusion

In this study, it was demonstrated that EPO reached the retinal ganglion cell layers when administered subconjunctivally. EPO reached the retina 24 h after the subconjunctival administration, and was still present 60 h after the administration. Furthermore, it was also proved that EPO subconjunctival administration did not cause any haematopoietic significant side-effects. The subconjunctival route was shown to be a promising alternative for EPO ocular delivery.     

Assessment of age changes and repeatability for computer-based rod dark adaptation

Purpose

To characterize the rate of rod-mediated sensitivity decline with age using a PC-driven cathode ray tube (CRT) monitor. To provide data regarding the repeatability of the technique.

Methods

Dark adaptation was monitored for 30 min following a minimum 30 % pigment bleach, using a white 1° stimulus (modulated at 1 Hz), presented 11° below fixation on a CRT monitor. Thirty-three subjects with no ocular pathology and normal fundus photographs were divided into two groups: older (≥45, n?=?16) and younger (<45, n?=?17).

Results

Rod recovery was assessed using component S2 of dark adaptation. S2 was significantly slower in the older (0.19?±?0.03 log cd.m^?2.min^?1) compared with the younger group (0.23?±?0.03 log cd.m^?2.min^?1, t?=??4.05, p?<?0.0003), despite no difference in visual acuity and fundus appearance. Faster rates of S2 recovery were correlated with lower threshold at 30 min (T₃₀) (r?=??0.49). Correlation coefficients between first and second measurements for S2 and T₃₀ were 0.49 (p?<?0.009) and 0.84 (p?<?0.0001) respectively. The coefficient of repeatability was 0.07 log cd.m^?2.min^?1 for S2 and 0.35 log cd.m^?2 for T₃₀. The coefficients of variation for S2 and T₃₀ were 15 % and 10 % respectively.

Conclusions

Dark adaptation is slowed in normal ageing. CRT-based dark adaptometry is easily implemented and highly repeatable. The technique described in this article would be useful for documenting visual changes in future clinical trials assessing retinal health in the older eye with and without ocular pathology.