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British Journal of Ophthalmology current issue



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Highlights from this issue

2017-12-15T04:50:35-08:00

Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity (see page 14)

Early hyperglycemia is significantly, and independently, associated with development of treatment-demanding Retinopathy of Prematurity, when adjusted for known risk factors.

Outcomes of penetrating keratoplasty in congenital hereditary endothelial dystrophy (see page 19)

Congenital hereditary endothelial dystrophy (CHED) is a rare condition. This study demonstrated a poor outcome from penetrating keratoplasty for CHED in Irish patients due to dense amblyopia and a high risk of graft failure.

Emergency corneal grafting in the UK: a 6-year analysis of the UK transplant registry (see page 26)

The information available about emergency corneal graft surgery is limited. In this study, 6 years of data were analysed from UK Blood & Tissue transplant. Emergency corneal graft surgery, although less successful than routine corneal graft surgery, was observed to be a successful eye and sight...




ROCK inhibitors for the treatment of ocular diseases

2017-12-15T04:50:35-08:00

The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of multiple ocular and systemic disorders. Recently, ROCK inhibitors have been suggested as novel treatments for various ocular diseases. Several in vitro, in vivo and clinical studies have demonstrated the safety and efficacy of ROCK inhibitors in the management of ocular disorders such as corneal epithelial and endothelial damage, glaucoma, retinal and choroidal neovascularisation, diabetic macular oedema and optic nerve disorders. In this review, these studies are explored with focus on the relevant clinical investigations.




Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas

2017-12-15T04:50:35-08:00

Introduction

Currently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host’s genome can be detected in the same small amount of ocular fluid.

Methods

In this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations.

Results

MDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma.

Conclusion

MDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas.




A worldwide survey of retinopathy of prematurity screening

2017-12-15T04:50:35-08:00

Background

To ascertain which countries in the world have retinopathy of prematurity (ROP) screening programmes and guidelines and how these were developed.

Methods

An email database was created and requests were sent to ophthalmologists in 141 nations to complete an online survey on ROP screening in their country.

Results

Representatives from 92/141 (65%) countries responded. 78/92 (85%) have existing ROP screening programmes, and 68/78 (88%) have defined screening criteria. Some countries have limited screening and those areas which have no screening or for which there is inadequate knowledge are mainly Southeast Asia, Africa and some former Soviet states.

Discussion

With the increasing survival of premature babies in lower-middle-income and low-income countries, it is important to ensure that adequate ROP screening and treatment is in place. This information will help organisations focus their resources on those areas most in need.




Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity

2017-12-15T04:50:35-08:00

Background

To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP).

Methods

This is a Danish national, retrospective, case–control study of premature infants (birth period 2003–2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential ‘new’ risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex).

Results

Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031).

Conclusion

An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors.




Outcomes of penetrating keratoplasty in congenital hereditary endothelial dystrophy

2017-12-15T04:50:35-08:00

Background/aim

To report the outcome of penetrating keratoplasty (PKP) in Irish patients with congenital hereditary endothelial dystrophy (CHED).

Methods

A retrospective case series review of patients with CHED who underwent PKP was conducted. The outcomes of PKP in 14 patients with CHED at the Royal Victoria Eye and Ear Hospital in Dublin from 1978 to 2013 were described following case note review. The main outcome measures were best-corrected visual acuity (BCVA) and graft survival.

Results

Thirty-three corneal transplants were performed, which included 32 PKPs and one Descemet’s stripping endothelial keratoplasty. Twenty-four eyes underwent primary corneal grafts and nine eyes had regrafts. The graft survival rates at final follow-up were 37.5% and 33% in the primary graft and regraft groups, respectively. Preoperative BCVA was 20/200 or worse in all patients. At the final postoperative visit, the BCVA was 20/80 or better in four eyes following primary PKP, 20/160 in one eye following regrafting and was 20/200 or worse in all other eyes. The mean time to graft failure was 16 months (range 0–37 months). The mean follow-up time was 101 months (range 12–252 months). Fifty per cent of the patients continue to attend for follow-up.

Conclusions

This study has demonstrated a poor outcome from PKP for CHED in this Irish cohort. This arises from a combination of dense amblyopia and a high risk of graft failure in the long term.




Emergency corneal grafting in the UK: a 6-year analysis of the UK Transplant Registry

2017-12-15T04:50:35-08:00

Background

Corneal graft (CG) surgery is the most common and successful tissue transplant worldwide. A small and important group of patients are operated in emergency situations, typically to save a perforated eye. Our knowledge of the indications and outcomes of emergency corneal graft (eCG) is limited.

Methods

Retrospective, multifactorial analysis of all CGs registered by the UK Transplant Service from April 1999 to March 2005.

Results

A total of 12 976 CGs were performed. 1330 (11.4%) were eCGs including 433 regrafts. Actual perforation occurred in 876 (65.9%) patients. 420 (31.5%) grafts were for tectonic purposes alone and 217 (16.3%) were also grafted for visual rehabilitation. The main diagnostic categories were infection (39.4%), non-infectious ulcerative keratitis (32.2%) and other causes (ectasias, previous ocular surgery, injury, dystrophies and opacification). Graft survival of first eCG at 1, 2 and 5 years was 78%, 66% and 47%, respectively. Best-corrected visual acuity of surviving grafts at 1 year was: 6/12 or better in 29.9%, 6/18 to 6/60 in 38.4%, counting finger to LP in 30.6% and NPL in 1%, with worsening of vision in only 8.7% of the patients.

Conclusion

This study which is the largest of its kind shows that despite the seriousness of the critical corneal pathology and the surgical challenges that it poses, the outcomes of eCG are favourable with most patients keeping their eyesight and avoiding immediate rejection. These clinical outcomes show the value of eye banking facilities that are developed to support corneal tissue supply for eCG.




Long-term clinical outcome of femtosecond laser-assisted lamellar keratectomy with phototherapeutic keratectomy in anterior corneal stromal dystrophy

2017-12-15T04:50:35-08:00

Purpose

To evaluate long-term outcome of femtosecond laser-assisted lamellar keratectomy (FLK) with phototherapeutic keratectomy (PTK) in patients with anterior corneal stromal dystrophies.

Methods

A total of 10 eyes from seven patients who underwent FLK were included. The patients had suffered from recurrent corneal erosion or visual disturbance in anterior corneal dystrophies (five Avellino dystrophies and two lattice dystrophies). Planar-shaped lamellar keratectomy was performed using femtosecond laser. The amount of corneal excision was determined by the depth of corneal opacity. Additional PTK with mitomycin C application was performed for smoothening of corneal cut surface. The patients were evaluated with following parameters: uncorrected visual acuity, best-corrected visual acuity (BCVA), mean anterior keratometric value, corneal irregularity, corneal high-order aberrations (HOA) and the recurrence of corneal erosion.

Results

Mean duration of follow-up was 64 months (2.5–9.5 years). The BCVA improved more than two lines of Snellen chart at last visit. The changes of keratometric values were within ±1 D in eight out of 10 eyes. Corneal irregularities in central 5 mm cornea and the values of total corneal HOA in central 6 mm cornea decreased by 0.3–3.1 D and 0.01–2.2 µm, respectively. Corneal erosion did not recur in any of those patients during follow-up and corneal dystrophy did not recur in eight out of 10 eyes.

Conclusion

In anterior corneal stromal dystrophies, FLK with PTK can be an effective surgical option to improve VA through decreasing corneal irregularities and HOA, while minimising corneal curvature changes.




Stability of visual outcome between 2 and 5 years following corneal transplantation in the UK

2017-12-15T04:50:35-08:00

Background and Aims

Many studies of corneal transplantation focus on graft failure or rejection as endpoints, or report visual outcomes at one postoperative time point. We aimed to study the stability of visual outcomes between 2 and 5 years following corneal transplantation.

Methods

All patients with keratoconus (868) or Fuchs endothelial dystrophy (FED) (569) receiving their first corneal transplant for visual purposes in the UK between January 2003 and December 2009 were included. The probability of visual improvement or deterioration (gain or loss of ≥2 Snellen lines, respectively) between 2 and 5 years after keratoplasty was modelled by multivariable logistic regression.

Results

The majority of keratoconus patients with a penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty maintained their visual acuity (651/868; 75%) while 15% (133/868) improved and 10% (84/868) deteriorated. Similarly, most patients with FED who received a PK maintained their vision (395/569; 70%) while 18% (105/569) improved and 12% (68/569) deteriorated.




Comparison of corneal dynamic parameters and tomographic measurements using Scheimpflug imaging in keratoconus

2017-12-15T04:50:35-08:00

Aim

To compare the diagnostic ability of corneal tomography and corneal dynamic response measurements in normal and keratoconus eyes.

Methods

Consecutive patients with grade II–III keratoconus and age-matched normal subjects were recruited. Corneal imaging was performed using Pentacam (Oculus Optikgeräte, Wetzlar, Germany) and Corvis (Oculus Optikgeräte). A beta version of Corvis software was used with three additional parameters: maximal change of arc length, deformation amplitude (DA) ratio 1 and DA ratio 2. Diagnostic ability of both devices to differentiate normal and keratoconus eyes was evaluated using receiver-operating characteristic (ROC) curves. The areas under the ROC curve (AUC) and partial AUC (pAUC) for specificity ≥80% for each parameter of Corvis and final D value of Belin/Ambrosio Enhanced Ectasia Display (BAD) were compared.

Results

Forty-two eyes of 42 patients (21 patients with keratoconus and 21 normal subjects) were included. Both groups were age matched (p=0.760). The ROC analysis showed that the final D value of BAD had the highest AUC (0.994) and pAUC (0.194). Maximum inverse radius had the highest AUC (0.954) but a relatively lower pAUC (0.158), while DA ratio 2 had the second highest AUC (0.946) together with the highest pAUC (0.177) among Corvis parameters. There was no significant difference between AUC and pAUC of BAD compared with those of DA ratio 1 (p≥0.162) and DA ratio 2 (p≥0.208).

Conclusions

The results of our study suggest that Corvis measurements have the potential to differentiate keratoconus and normal eyes. The diagnostic ability of novel parameters on Corvis was comparable to Pentacam.




Long-term outcomes of the Boston type I keratoprosthesis in eyes with previous herpes simplex virus keratitis

2017-12-15T04:50:35-08:00

Purpose

To report the long-term outcomes of the Boston type I keratoprosthesis (Kpro) in eyes with prior herpes simplex virus (HSV) keratitis.

Methods

Retrospective review of all Kpro procedures performed by a single surgeon from 1 May 2004 to 1 January 2015.

Results

13 of 173 Kpro procedures were performed in 11 eyes with prior HSV keratitis. There was not a significant difference in the percentage of eyes with and without prior HSV keratitis with preoperative (9% vs 8%, p=1.00) or postoperative (57% vs 60%, p=1.00) corrected distance visual acuity (CDVA) ≥20/200 or in the percentage of contralateral eyes with preoperative CDVA ≥20/50 (55% vs 30%, p=0.18). While several postoperative complications occurred approximately twice as often in eyes with prior HSV keratitis, including persistent epithelial defect (63.6% vs 34.1%; p=0.10), corneal infiltrate (27.3% vs 12.3%; p=0.17) and sterile vitritis (18.2% vs 9.4%; p=0.31), only cystoid macular oedema (45.5% vs 12.3%; p=0.01) was significantly more common. Similarly, while the Kpro retention failure rate in eyes with prior HSV keratitis was twice than that in eyes without it (0.15 vs 0.07 per year), the difference was not statistically significant (p=0.09).

Conclusion

As greater than half of patients with unilateral HSV keratitis undergoing Kpro implantation have CDVA ≥20/50 in the contralateral eye, and as the Kpro retention failure rate in eyes with prior HSV keratitis is twice than that in eyes without prior HSV keratitis, caution should be exercised when considering Kpro implantation in these patients.




Conjunctival lymphangiectasia associated with classic Fabry disease

2017-12-15T04:50:35-08:00

Background

Fabry disease (FD) is a treatable multisystem disease caused by a defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal verticillata, are among the earliest diagnostic findings. Conjunctival lymphangiectasia (CL) has not previously been associated with FD.

Methods

We examined the eyes of a cohort of 13 adult patients, eight men and five women, with documented classic FD, all treated with enzyme replacement therapy (ERT) at the University of Alabama at Birmingham between February 2014 and April 2015. The average age was 48 years with a range of 35–55 years for men and 21–71 years for women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years) with a range of 4–14 years. Classical Fabry mutations included Q283X, R227X, W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap imaging system was used to record conjunctival images.

Results

CL was observed in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations included single cysts, beaded dilatations and areas of conjunctival oedema. Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects (77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were symptomatic, and 10 had peripheral lymphoedema.

Conclusion

CL represents a common but under-recognised ocular manifestation of FD, which persists despite ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.




Growth of meibomian gland tissue after intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction

2017-12-15T04:50:35-08:00

Purpose

To investigate the impact of meibomian gland probing (MGP) on meibomian gland (MG) area from the upper lids of patients with obstructive meibomian gland dysfunction (o-MGD).

Methods

Retrospective study comparing pre-MGP/post-MGP non-contact infrared meibography results in patients with o-MGD, viewing signs of MG growth within total measurement field.

Results

Post-MGP meibography of 34 lids (19 patients, ≥4.5 to ≤12 months’ follow-up) showed 41.2% with MG growth. Ten lids had meibographies suitable for analysis, showing significant collective (116 glands) increase in mean individual glandular area (MIGA) of 4.87% (p=0.0145). Four of 10 lids independently showed significant increase in MIGA, ranging from 10.70% to 21.13% (p<0.0001, p=0.0277, p=0.0292, p=0.0345), while six did not.

At >12 and <25 months’ follow-up, 16 lids (9 additional patients) had follow-up showing 25% with signs of MG growth. Analysis of three lids showed a significant collective (33 glands) increase in MIGA of 11.19% (p=0.0004). Two of three lids independently showed significant increase in MIGA of 13.73% and 20.00% (p=0.0097, p=0.0001). Collectively, for all 13 analysed lids (149 glands), there was a significant increase of 6.38% in total glandular area (p=0.0447) and a significant increase of 6.23% in MIGA (p=0.0003).

Conclusion

MGP was associated with increased MG tissue area and growth of atrophied MGs as viewed on meibography. MGP provides unequivocal physical proof of a patent meibum outflow tract through the natural orifice, and may promote glandular growth in part by direct mechanical establishment of a patent duct/orifice system.




Long-term outcomes of orbital fat decompression in Graves orbitopathy

2017-12-15T04:50:35-08:00

Purpose

To evaluate the long-term clinical efficacy of orbital fat decompression in treating proptosis in Graves' ophthalmopathy (GO).

Methods

Retrospective review of 1604 eyes of 845 patients with symmetric (1518 eyes) and asymmetric (86 eyes) proptosis who received orbital fat decompression between 2003 and 2014. Changes in Hertel values were evaluated at baseline, 6 months postoperatively and yearly thereafter. Recurrence of proptosis, diplopia and other complications that required additional surgeries were documented and analysed. The surgical outcome was defined as complete success if there was proptosis reduction with no recurrence and improved or no diplopia. Partial success was considered if there was proptosis reduction without recurrence yet persistent or new-onset diplopia. Failure was considered if there was recurrence of proptosis regardless of diplopia. The patient’s quality of life was also evaluated as a long-term outcome.

Results

After follow-up for 37.9±24.4 months, 1365 eyes (85.1%) achieved complete success, 219 eyes (13.7%) achieved partial success and 20 eyes (1.2%) had failure. Newly onset diplopia and secondary decompression occurrence rate remained low at 3.3% and 0.6%, respectively. The total proptosis reduction was 4.1±1.3 mm, which was consistent all through the intermediate and long-term (5–10 years) follow-up. The amount of orbital fat removal (4.5±1.1 mL) played a significant role in the long-term Hertel change. Importantly, the overall quality of life increased significantly for GO patients after undergoing orbital fat decompression.

Conclusions

Orbital fat decompression has a long-term efficacy in correcting disfiguring proptosis with a low complication rate and without the need of secondary decompression procedures. This was also associated with a significant improvement in quality of life.




Use of Ruthenium-106 Brachytherapy for Iris Melanoma: The Scottish Experience

2017-12-15T04:50:35-08:00

Purpose

To analyse long-term outcomes of ruthenium-106 (106Ru) plaque brachytherapy for the treatment of iris melanoma.

Methods

We retrospectively reviewed medical records of 19 consecutive patients with pure iris melanoma treated with 106Ru plaque brachytherapy between 1998 and 2016 at the Scottish Ophthalmic Oncology Service, Glasgow. The iris melanoma was treated with a ruthenium plaque placed on the corneal surface to deliver a surface dose of 555 Gy. We analysed vision preservation, local tumour control, radiation-related complications, eye retention rates, symptomatic metastasis and melanoma-related mortality.

Results

The mean largest basal diameter of the lesions was 3.50±1.42 mm (range 1.6–6.5 mm), and the mean maximum height was 1.47±0.65 mm (range 0.7–2.8 mm). The tumour control and eye retention were 100% at a mean follow-up of 62 months (range 6–195 months). A 62% reduction in tumour height was observed on ultrasonography. Complications included cataract (68%), dry eye (47%), uveitis (37%) and scleral thinning (5%). At the final follow-up visit, the mean loss of Snellen visual acuity was 1.11±2.90 lines and vision of 6/9 or better was maintained in 53% of patients. None of the patients had evidence of symptomatic metastasis (non-imaged) or melanoma-related mortality.

Conclusions

106Ru plaque treatment for iris melanoma was highly effective a high tumour control, no tumour recurrences and a relatively a low complication rate.




Incidence and prevalence of uveitis in South Korea: a nationwide cohort study

2017-12-15T04:50:35-08:00

Aim

To evaluate the incidence and prevalence of uveitis and associated risk factors in South Korea.

Methods

For this retrospective national cohort study, approximately 1 000 000 Korean residents were randomly selected from the Korean National Health Insurance Service database. Uveitis was defined according to the Korean Classification of Diseases. The uveitis incidence and prevalence were calculated. Sociodemographic factors and comorbidities associated with uveitis were evaluated via Cox proportional regression models.

Results

A total of 1 094 440 subjects were evaluated over 7 051 346 person-years (mean follow-up: 6.44 years). Overall, 7447 newly developed uveitis cases were identified during the period of 2007–2013; the average incidence of uveitis was 10.6 per 10 000 person-years (95% CI 10.3 to 10.8). The average incidences of anterior and non-anterior uveitis were 9.0 and 1.5 per 10 000 person-years, respectively. The prevalence rates of uveitis, anterior uveitis and non-anterior uveitis were 17.3, 15.0 and 2.3 per 10 000 persons, respectively, during the period of 2007–2013. Increasing age, male sex, residing in a relatively rural area and high income were associated with uveitis, along with Behcet’s disease, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematous, ulcerative colitis and tuberculosis.

Conclusions

The overall incidence of uveitis in Korea was similar to those reported in Taiwan and the USA. Despite a potentially inaccurate disease definition, claims data may be useful for monitoring the substantial uveitis burden in South Korea.




Progression of lamellar hole-associated epiretinal proliferation and retinal changes during long-term follow-up

2017-12-15T04:50:35-08:00

Purpose

To report on progression of lamellar hole-associated epiretinal proliferation (LHEP) in eyes with lamellar macular holes (LMH) using spectral-domain optical coherence tomography (SD-OCT), and to correlate with intraretinal changes and visual function.

Methods

From a retrospectively reviewed series of 167 eyes with non-full-thickness macular holes, we exclusively included a subgroup of 34 eyes with LMH and LHEP by SD-OCT evaluation. In these eyes, area of LHEP, intraretinal changes of defect diameter, central retinal thickness, defects of the ellipsoid zone and occurrence of a contractive epiretinal membrane were analysed. Additionally, clinical data were documented.

Results

Area of LHEP significantly increased during a mean follow-up period of 40.5 months (median 52 months). Analysing intraretinal changes, a significant enlargement of minimum and maximum horizontal lamellar hole diameter was found that correlated with the area of LHEP. Defects of the ellipsoid zone were seen in 65% of the eyes at baseline and in 85% at the end of follow-up. Increase of maximum horizontal hole diameter and ellipsoid zone defects correlated with a decline of visual acuity. Fifty per cent of patients with LMH and LHEP also demonstrated extrafoveal typical contractive epiretinal membranes with retinal folds.

Conclusions

Long-term follow-up revealed an increase of the area of LHEP in eyes with LMH that correlated with the enlargement of lamellar hole diameter and ellipsoid zone defects. Our data delineate the progression of intraretinal changes in association with a decline of visual function in this subgroup of LMH eyes.




One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration

2017-12-15T04:50:35-08:00

Aim

To evaluate 12-month outcome of intravitreal ziv-aflibercept (IVZ) therapy in eyes with neovascular age-related macular degeneration (nAMD) that are non-responsive to bevacizumab and ranibizumab.

Methods

This retrospective study included 16 eyes (14 patients) with nAMD who were on prior treatment with bevacizumab and ranibizumab and were treated with as-needed IVZ (1.25 mg/0.05 mL) for 12 months. The primary outcome measure was the mean change in best corrected visual acuity (BCVA) and secondary outcome measures included mean change in central macular thickness (CMT), retinal pigment epithelial detachment (RPED) heights, longest treatment free interval, presence of subretinal fluid (SRF) and intraretinal fluid (IRF) and adverse events.

Results

There was no change in the mean logarithm of minimum angle of resolution (logMAR) BCVA at baseline and following treatment with IVZ therapy (p=0.978). The mean number of IVZ injections during 12 months was 5.9±3.3, and the mean number of antivascular endothelial growth factors (VEGFs) injections prior to switching to IVZ was 8.4±4.7. The mean treatment free interval was longer during IVZ therapy (114.4±67.1 days) compared with 76.3±54.6 days before IVZ therapy (p=0.03). Five (31.25%) eyes had visual gains of at least 0.1 logMAR, 3 (18.75%) eyes had stable BCVA (within 0.1 logMAR) and 8 (50%) eyes had BCVA decline of at least 0.1 logMAR. There was no significant difference in the mean CMT, RPED heights and presence of IRF and SRF at 12 months compared with baseline. No adverse events were noted.

Conclusion

IVZ increased the treatment free interval in non-responders but no significant change in visual and anatomic outcomes.




Six-year outcomes of antivascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy

2017-12-15T04:50:35-08:00

Objective

To evaluate the 6-year outcomes of anti-VEGF (vascular endothelial growth factor) monotherapy for polypoidal choroidal vasculopathy (PCV).

Methods

The charts of 66 eyes of 66 patients with newly diagnosed, symptomatic, treatment-naive PCV were reviewed retrospectively. All patients were treated with 0.5 mg intravitreal ranibizumab (IVR) injections for 3 months followed by as-needed reinjections based on monthly examinations until 3 years after the first IVR injection. Thereafter, anti-VEGF monotherapy was continued for another 3 years.

Results

The mean best-corrected visual acuity (BCVA) improved significantly (p=0.001) 3 months after the first IVR injection (0.24±0.30 logarithm of the minimum angle of resolution (logMAR) VA; 20/35 Snellen VA) compared with the baseline BCVA (0.34±0.37 logMAR VA; 20/44 Snellen VA). However, the improved VA returned to 0.32±0.39 logMAR unit (20/42 Snellen VA), which was not significantly different at 3 years. This level was maintained to the end of 6 years (0.36±0.37 logMAR unit; 20/46 Snellen VA). The mean numbers of anti-VEGF injections administered annually during 6 years were 5.6±2.4 (including the initial three monthly injections), 3.3±2.2, 3.3±2.9, 3.6±3.2, 3.5±2.9 and 3.3±2.7, respectively. The mean total number of injections during 6 years was 21.5±10.1.

Conclusions

The results emphasised the efficacy of anti-VEGF therapy for preserving vision and the limitations of anti-VEGF therapy in that continuous treatment is required over an extended follow-up period.




Visual and ocular motor function in the atypical form of neurodegeneration with brain iron accumulation type I

2017-12-15T04:50:35-08:00

Background/aims

Neurodegeneration with brain iron accumulation (NBIA) type I is a rare disease that can be divided into a classical or atypical variant, according to age of onset and clinical pattern. Neuro-ophthalmological involvement has been documented in the classical variant but only anecdotically in the atypical variant. We sought to describe the visual and ocular motor function in patients with atypical form of NBIA type I.

Methods

Cross-sectional study, including patients with genetically confirmed NBIA type I and classified as atypical variant, who underwent ophthalmological examination with best corrected visual acuity (BCVA), optical coherence tomography (OCT), fundus autofluorescence (FAF), electroretinography (ERG), visual evoked potentials (VEP) and video-oculography.

Results

Seven patients with a mean BCVA of 0.12±0.14 logMAR were included. Only two patients showed structural evidence of advanced retinopathy in OCT and FAF, and there were no cases of optic atrophy. ERG data, however, showed abnormal scotopic and/or photopic responses in all patients. VEP were normal in all three patients. Ocular fixation was markedly unstable (eg, increased rate of saccadic pulses) in the majority of patients (5). Additional mild ocular motor disturbances included low gain pursuit (2), hypermetric saccades (1), low gain optokinetic (2) and caloric and rotatory responses (3).

Conclusion

Functional retinal changes associated with marked instability of ocular fixation should be included in the clinical spectrum of NBIA, particularly in the atypical form.




Interdevice comparison of retinal sensitivity assessments in a healthy population: the CenterVue MAIA and the Nidek MP-3 microperimeters

2017-12-15T04:50:35-08:00

Background

To compare and correlate the retinal sensitivity measurements obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity Assessment (MAIA) microperimeters among healthy subjects.

Methods

In this prospective comparative study, 31 eyes of 23 subjects underwent complete ophthalmological examination including retinal sensitivity assessments using two microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log units) were analysed between the two instruments. The interdevice reproducibility and level of agreement between the sensitivity values of the devices were assessed.

Results

The mean retinal sensitivity (dB) measured by the MP-3 (25.02±1.06 dB, range: 20.90–26.70) was significantly (p<0.0001) lower compared with the MAIA (30.68±0.74 dB, range: 28–31.84). The luminosity levels were significantly (p<0.0001) higher with the MP3 (7.75±1.31 asb, range: 6.44–9.06) compared with the MAIA (0.92±0.14 asb, range: 0.78–1.06). The contrast sensitivity was significantly higher for the MP-3 (0.94±0.33 log units, range: 0.61–1.27) compared with the MAIA (0.23±0.03 log units, range: 0.20–0.26). Despite these absolute differences, the intraclass coefficient was 0.85 (95% CI 0.70 to 0.92) between the two devices after applying a standard correction factor to each data point (MAIA sensitivity=MP-3 sensitivity+5.65) with a mean difference between MAIA and MP-3 of 0.01.

Conclusion

Retinal sensitivity measures higher, but luminance and contrast sensitivity measure lower for MAIA-generated values compared with the MP-3. The relationships, however, appeared fairly consistent, and application of a standard correction factor allowed the data to be inter-related, at least for normal eyes.




Electrophysiological findings show generalised post-photoreceptoral deficiency in macular telangiectasia type 2

2017-12-15T04:50:35-08:00

Background

Photoreceptor damage, reported in single observations, has been suggested to contribute to the disease pathogenesis in macular telangiectasia type 2 (MacTel2). The purpose of this study was to ascertain whether the photoreceptor or post-photoreceptoral function is affected in MacTel2 and could be detected using electrophysiological examination.

Methods

Thirty-five eyes from 18 patients (15 men, aged 60.1±9.6 years, range 38–77 years) with MacTel2 were included in the study. All patients underwent standard ophthalmic examination followed by pattern electroretinography (PERG) and full-field ERG. The data were compared against 22 normal control subjects (10 men, age 59.83±6.28 years, range 48–76).

Results

Mean PERG P50 amplitude and peak time in patients with MacTel2 did not differ significantly from control values (p>0.2) but P50 amplitude was subnormal in three patients. The mean scotopic rod b-wave amplitude was significantly lower in patients than in healthy controls (p=0.027). A lower dark-adapted 10.0 b-wave (p=0.06) but not a-wave amplitude (p=0.58) was present in patients with MacTel2. Photopic single-flash a-wave and b-wave amplitudes did not differ between patient and control groups (p=0.2 and 0.3), but 30 Hz flicker peak time was significantly later in patients with MacTel2 with no effect on amplitude (p=0.04 and 0.7).

Conclusion

Both scotopic (rod system dominated) and photopic ERGs (cone system) are consistent with post-photoreceptoral dysfunction. There was no electrophysiological evidence of dysfunction at the level of the photoreceptor.




Peripheral leptochoroid: clinical and anatomical findings

2017-12-15T04:50:35-08:00

Background/Aims

To investigate the clinical findings and anatomical characteristics of patients with a thinned peripheral choroid (leptochoroid) presenting with bilateral macular geographical hyperpigmented fundus and compare with matched controls.

Methods

A retrospective, observational case series of 44 eyes (24 patients): 22 study eyes (12 study patients) with clinical findings of leptochoroid (geographical hyperpigmented fundus centred in the macula) matched with 22 control eyes (12 control patients). All eyes received enhanced depth imaging optical coherence tomography at Memorial Sloan Kettering Cancer Center. Two independent observers performed all measurements. Statistical analysis was used to correlate interobserver findings, and compare patient and eye characteristics.

Results

Study patients had a female predominance and median age of 70 years. Iris colour and refractive error of these eyes were varied: 8 eyes were myopic (one of which was highly myopic with a refractive error of –9.00) and 14 eyes were emmetropic or hyperopic (up to+3.00). The best-corrected visual acuity was 20/40 or better in all study eyes. The geographical macular areas of relative hyperpigmentation correspond to normal choroidal thickness compared with controls (p=0.74). The relative hypopigmented surrounding fundus had significantly thinner choroid compared with controls (p value=0.0001). Choroidal thickness had a strong interobserver correlation (r=0.99, p<0.0001).

Conclusion

Described here is a clinical entity referred to as peripheral leptochoroid. It appears as geographical hyperpigmented fundus centred in the macula, with adjacent relative hypopigmented fundus. Compared with matched normal subjects, the hyperpigmented and hypopigmented fundus correspond with equivocal and decreased choroidal thickness, respectively.




Assessing total retinal blood flow in diabetic retinopathy using multiplane en face Doppler optical coherence tomography

2017-12-15T04:50:35-08:00

Aim

To assess total retinal blood flow (TRBF) in diabetic retinopathy (DR) using multiplane en face Doppler optical coherence tomography (OCT).

Methods

A 70 kHz spectral-domain OCT system scanned a 2x2 mm area centred at the optic disc of the eyes with DR and healthy participants. The multiplane en face Doppler OCT algorithm generated a three-dimensional volumetric data set consisting of 195 en face planes. The TRBF was calculated from the maximum flow values of each branching retinal vein at an optimised en face plane. DR severity was graded according to the international clinical classification system. The generalised linear model method was used to compare flow values between DR groups and the control group.

Results

A total of 71 eyes from 71 participants were included. Ten eyes were excluded due to poor image quality. The within-visit repeatability of scans was 4.1% (coefficient of variation). There was no significant difference in the TRBF between the healthy (46.7±10.2 µL/min) and mild/moderate non-proliferative DR (44.9±12.6 µL/min) groups. The TRBF in severe non-proliferative DR (39.1±12.6 µL/min) and proliferative DR (28.9±8.85 µL/min) groups were significantly lower (p=0.04 and p<0.0001, respectively) than that of the healthy group. TRBF was correlated with DR disease severity (p<0.0001, linear trend test).

Conclusion

The novel multiplane en face Doppler OCT method provided reliable measurements of TRBF in DR eyes. This may be a useful tool in understanding the pathophysiology of DR.




Effect of acute intraocular pressure elevation on the minimum rim width in normal, ocular hypertensive and glaucoma eyes

2017-12-15T04:50:35-08:00

Background

To estimate and compare changes in the Bruch’s membrane opening—minimum rim width (BMO–MRW) and area in normal, ocular hypertensive and glaucoma eyes following acute elevations in intraocular pressure (IOP).

Methods

The optic nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and 53 with primary glaucoma) were imaged using Spectral-domain optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and ONH was rescanned with OCT. In each OCT volume, BMO–MRW and area were calculated and at each IOP increment.

Results

The baseline MRW was significantly smaller in glaucoma subjects (174.3±54.3 µm) compared with normal (287.4±42.2 µm, p<0.001) and OHT subjects (255.4±45.3 µm, p<0.001). MRW of glaucoma subjects was significantly thinner at the first and second IOP elevations than that at baseline (both p<0.01), but no significant change was noted in normal and OHT subjects. There was no significant change of BMO area at acute IOP elevations from baseline in all diagnoses (all p>0.05).

Conclusion

Acute IOP elevation leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma subjects only without changing ONH size. This suggests that the neural and connective tissues at ONH level in glaucoma subjects are more susceptible to acute IOP episodes than OHT or normal controls.




Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging

2017-12-15T04:50:35-08:00

Purpose

Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene.

Methods

Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants.

Results

Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic.

Conclusions

AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A. This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes.




In vitro synergy of natamycin and voriconazole against clinical isolates of Fusarium, Candida, Aspergillus and Curvularia spp

2017-12-15T04:50:35-08:00

Aim

To determine the minimum inhibitory concentrations (MICs) of voriconazole and natamycin, alone and in combination, against the clinical isolates of Fungus and to evaluate the synergy between the drugs in an experimental in vitro study.

Methods

In an experimental in vitro study, clinical isolates of Fusarium, Aspergillus, Candida and Curvularia spp were maintained on Sabouraud Dextrose Agar and used for the study. The MICs of natamycin and voriconazole, used alone and in combination, were evaluated by checkerboard microdilution technique based on the standard protocol proposed by the Clinical Laboratory Standards Institute. The interactions were assessed using the fractional inhibitory concentration (FIC) Index model.

Results

Tested with all the clinical isolates, the MICs ranged between 0.125 and 8 µg/mL both for natamycin and voriconazole. In descending order, maximum synergism (FIC ≤0.5) was observed in Candida spp (33.3%) followed by Curvularia spp and Fusarium spp (23.1%). Synergism was least for Aspergillus spp (22.2%). However, at 61.5% (8/13), maximum additive effect (>0.5–1) was observed in Aspergillus spp and minimum (33.3%, 2/6) in Candida spp. Indifference (FIC value >1 and≤4) was observed in 22.2% (2/9) of Aspergillus spp, 15.4% (2/13) of Fusarium spp, 33.3% (2/6) of Candida spp and 23.1% (3/13) of Curvularia spp. No cases of antagonism (FIC >4) were observed.

Conclusions

Natamycin and voriconazole in combination demonstrated more effective antifungal activity than single-use in vitro treatment in all species tested, which implies that these combinations may be helpful in treating fungal keratitis. There was no antagonism between these two drugs.




Multimodal imaging of small hard retinal drusen in young healthy adults

2017-12-15T04:50:35-08:00

Background

Small hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen.

Methods

Retinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised.

Results

Small hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22–61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex.

Conclusion

High lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1–4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.