Macular Abnormality Observed by OCT in Children with Amblyopia Failing to Achieve Normal Visual Acuity After Long-Term Treatment

Abstract Background The neuronal ceroid lipofuscinoses (CLN diseases) are fatal lysosomal storage diseases causing neurodegeneration in the CNS. We have previously shown that neuroinflammation comprising innate and adaptive immune reactions drives axonal damage and neuron loss in the CNS of palmitoyl protein thioesterase 1-deficient (Ppt1−/−) mice, a model of the infantile form of the diseases (CLN1). Therefore, we here explore whether pharmacological targeting of innate immune cells modifies disease outcome in CLN1 mice. Methods We applied treatment with PLX3397 (150 ppm in the chow), a potent inhibitor of the colony stimulating factor-1 receptor (CSF-1R) to target innate immune cells in CLN1 mice. Experimental long-term treatment was non-invasively monitored by longitudinal optical coherence tomography and rotarod analysis, as well as analysis of visual acuity, myoclonic jerks, and survival. Treatment effects regarding neuroinflammation, neural damage, and neurodegeneration were subsequently analyzed by histology and immunohistochemistry. Results We show that PLX3397 treatment attenuates neuroinflammation in CLN1 mice by depleting pro-inflammatory microglia/macrophages. This leads to a reduction of T lymphocyte recruitment, an amelioration of axon damage and neuron loss in the retinotectal system, as well as reduced thinning of the inner retina and total brain atrophy. Accordingly, long-term treatment with the inhibitor also ameliorates clinical outcomes in CLN1 mice, such as impaired motor coordination, visual acuity, and myoclonic jerks. However, we detected a sex- and region-biased efficacy of CSF-1R inhibition, with male microglia/macrophages showing higher responsiveness toward depletion, especially in the gray matter of the CNS. This results in a better treatment outcome in male Ppt1−/− mice regarding some histopathological and clinical readouts and reflects heterogeneity of innate immune reactions in the diseased CNS. Conclusions Our results demonstrate a detrimental impact of innate immune reactions in the CNS of CLN1 mice. These findings provide insights into CLN pathogenesis and may guide in the design of immunomodulatory treatment strategies.

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Intravitreal bevacizumab monotherapy in myopic choroidal neovascularisation: 5-year outcomes for the PAN-American Collaborative Retina Study Group

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310411 ◽

2017 ◽

Vol 102 (4) ◽

pp. 455-459 ◽

Cited By ~ 3

Author(s):

Jay Chhablani ◽

Remya Mareen Paulose ◽

Andres F Lasave ◽

Lihteh Wu ◽

Cristian Carpentier ◽

...

Keyword(s):

Visual Acuity ◽

Adverse Events ◽

Real Life ◽

Intravitreal Bevacizumab ◽

Term Treatment ◽

Choroidal Neovascularisation ◽

Long Term Treatment ◽

The Mean

PurposeTo report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia.MethodsRetrospective analysis of naive CNV secondary to myopia that underwent antivascular endothelial growth factor monotherapy was performed. Collected data included demographic details, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last visit. Secondary outcomes included change in visual acuity, number of injections and adverse events.ResultsThirty-three eyes of 31 subjects with a mean age of 51.48±16.4 years were included. The mean follow-up was 66.47 months. 27 eyes had type 2 CNV and the rest seven eyes had type 1 CNV. The mean number of IVB injections per eye was 4.9. Mean visual acuity at baseline reduced from 0.65±0.33 logMAR units (Snellen equivalent=20/89) to 0.73±0.50 logMAR units (20/107) at final follow-up (p=0.003). The mean central macular thickness decreased from 309.31±86 µm at baseline to 267.5±70.89 µm at the last visit (p=0.03). However, visual acuity was maintained (±1 line of baseline) in 13 eyes (39.4%), ≥2 line improvement in nine (27.3%) eyes and more than two lines worsening in 11 eyes (33.3%). Foveal atrophy was observed at baseline and last visit in 6 (12.5%) and 14 (29.1%), respectively (p=0.007). No systemic adverse events were observed.ConclusionIVB monotherapy is safe and effective for long-term treatment of CNV secondary to myopia in real life.

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Coats’ disease: trends and long-term treatment outcomes in a tertiary referral centre

Therapeutic Advances in Ophthalmology ◽

10.1177/25158414211055957 ◽

2021 ◽

Vol 13 ◽

pp. 251584142110559

Author(s):

Avadhesh Oli ◽

Divya Balakrishnan ◽

Subhadra Jalali

Keyword(s):

Visual Acuity ◽

Treatment Outcomes ◽

Term Treatment ◽

Lower Stage ◽

Long Term Treatment ◽

Coats Disease ◽

The Mean ◽

Anatomical Outcomes

Background: The long-term treatment outcomes in Coat’s disease – particularly in the era of newer pharmacotherapies such as anti-vascular endothelial growth factor (VEGF) agents and depot steroids – are poorly understood. Aim: To describe the clinical features and treatment outcomes of 148 eyes with Coats’ disease assessed in a referral centre over 30 years. Materials and methods: We conducted a retrospective chart review of patients diagnosed with Coats’ disease between 1 June 1987 and 31 July 2017. The demographic, clinical and treatment data were collected and long-term functional and anatomical outcomes were analysed based on the treatment either with conventional therapy (cryo/laser) or along with adjuvants like intravitreal steroids or anti-VEGFs. Results: The mean age at presentation was 15.22 years (median 11). Familial exudative vitreoretinopathy was the most common referral diagnosis, 76/148 (51.5%), followed by Coats’ disease, 37/148 (25%), and retinoblastoma, 35/148 (23.6%). Stage 3B was most common at presentation (31.8%), followed by 2B (22.3%) and 2A (16.9%). A total of 107 patients were treated either with conventional therapy or in combination with adjuvants. The mean follow-up period was 24.95 months. The visual acuity improved from baseline logMAR 2.17 (Snellen-20/2958) to logMAR 1.88 (Snellen-20/1517) at final follow-up ( p = 0.004). The improvement in visual acuity was better when the presenting BCVA was <1 logMAR (Snellen 20/200), p = 0.004. No statistically significant change in BCVA was noted between conventional and adjuvant groups, p = 0.5. However, the final anatomical outcome was good in 78/99 (78.8%) in the conventional group and 45/49 (91.8%) in the adjuvant group, respectively ( p = 0.046). Conclusion: In this series of patients with Coats’ disease over three decades, the use of intravitreal steroids or anti-VEGFs as adjuvants resulted in better anatomical outcomes. A better baseline visual acuity, lower stage of the disease, and older age at presentation were found to be the factors leading to favourable visual outcomes. Summary In the current series of 148 eyes with Coats’ disease, adjuvant treatment with intravitreal steroids or anti-VEGFs resulted in better outcomes as compared with conventional cryotherapy or laser photocoagulation alone. Patients with Coats’ disease who had presented with better visual acuity at baseline, lower stage of the disease and older age had better final visual outcomes.

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