Review Article

Novel mitochondrial therapies for the treatment of age-related macular degeneration

Novel mitochondrial therapies for the treatment of age-related macular degeneration

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Abstract: The purpose of this article is to review current literature and data regarding treatment options for age-related macular degeneration (AMD) related to mitochondrial therapy. This article considers the presence of flavoprotein fluorescence as a potential biomarker to test the effectiveness of the treatments. We focus primarily on two major mitochondrial targets, nuclear factor erythroid 2-related factor (NFE2L2) and PGC-1α, that function in controlling the production and effects of reactive oxidative species (ROS) directly in the mitochondria. PU-91 is an FDA approved drug that directly targets and upregulates PGC-1α in AMD cybrid cell lines. Although neither NFE2L2 nor PGC1-α have yet been tested in clinical trials, their effects have been studied in rodent models and offer promising results. MTP-131, or elamipretide?, and metformin are two drugs in phase II clinical trials that focus on the treatment of advanced, non-exudative AMD. MTP-131 functions by associating with cardiolipin (CL) whereas metformin targets adenosine-monophosphate protein kinase (AMPK) in the mitochondria. The current results of their clinical trials are elucidated in this article. The molecular targets and drugs reviewed in this article show promising results in the treatment of AMD. These targets can be further pursued to improve and refine treatment practices of this diagnosis.

Abstract: The purpose of this article is to review current literature and data regarding treatment options for age-related macular degeneration (AMD) related to mitochondrial therapy. This article considers the presence of flavoprotein fluorescence as a potential biomarker to test the effectiveness of the treatments. We focus primarily on two major mitochondrial targets, nuclear factor erythroid 2-related factor (NFE2L2) and PGC-1α, that function in controlling the production and effects of reactive oxidative species (ROS) directly in the mitochondria. PU-91 is an FDA approved drug that directly targets and upregulates PGC-1α in AMD cybrid cell lines. Although neither NFE2L2 nor PGC1-α have yet been tested in clinical trials, their effects have been studied in rodent models and offer promising results. MTP-131, or elamipretide?, and metformin are two drugs in phase II clinical trials that focus on the treatment of advanced, non-exudative AMD. MTP-131 functions by associating with cardiolipin (CL) whereas metformin targets adenosine-monophosphate protein kinase (AMPK) in the mitochondria. The current results of their clinical trials are elucidated in this article. The molecular targets and drugs reviewed in this article show promising results in the treatment of AMD. These targets can be further pursued to improve and refine treatment practices of this diagnosis.

Case Report

A case of infectious endophthalmitis misdiagnosed as uveitis

A case of infectious endophthalmitis misdiagnosed as uveitis

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Abstract: Intraocular foreign body residue following ophthalmic surgery is rare but may cause severe postoperative occult inflammation. In some cases, small foreign bodies located in the anterior chamber angle may be missed by follow-up ultrasound biomicroscopy (UBM). We report the case of an elderly female whose right eye was injured by a nail and received corneal repair surgery in our hospital. Eleven days post-surgery, we found a mobile, short, translucent, rod-shaped foreign body in the upper corner of the right eye and another in the iris root at 7 o’clock. Two months post-surgery, the patient consulted a doctor due to right eye redness, pain, and vision loss, which was ultimately shown to be associated with foreign body residue resulting in a delayed postoperative inflammatory response. The patient was cured by surgeries and active anti-inflammatory and anti-infection treatments, but the final diagnosis of the patient was infectious endophthalmitis misdiagnosed as uveitis, which worths our consideration. We also review relevant literature on the differentiation of postoperative infectious endophthalmitis from noninfectious uveitis. It’s a reminder that patients with delayed endophthalmitis after open ocular trauma should not exclude the possibility of intraocular foreign bodies. As well clinicians can distinguish infectious endophthalmitis from uveitis by needle aspiration biopsy or vitrectomy for microbial culture in order to determine the need for antibiotic treatment.

Abstract: Intraocular foreign body residue following ophthalmic surgery is rare but may cause severe postoperative occult inflammation. In some cases, small foreign bodies located in the anterior chamber angle may be missed by follow-up ultrasound biomicroscopy (UBM). We report the case of an elderly female whose right eye was injured by a nail and received corneal repair surgery in our hospital. Eleven days post-surgery, we found a mobile, short, translucent, rod-shaped foreign body in the upper corner of the right eye and another in the iris root at 7 o’clock. Two months post-surgery, the patient consulted a doctor due to right eye redness, pain, and vision loss, which was ultimately shown to be associated with foreign body residue resulting in a delayed postoperative inflammatory response. The patient was cured by surgeries and active anti-inflammatory and anti-infection treatments, but the final diagnosis of the patient was infectious endophthalmitis misdiagnosed as uveitis, which worths our consideration. We also review relevant literature on the differentiation of postoperative infectious endophthalmitis from noninfectious uveitis. It’s a reminder that patients with delayed endophthalmitis after open ocular trauma should not exclude the possibility of intraocular foreign bodies. As well clinicians can distinguish infectious endophthalmitis from uveitis by needle aspiration biopsy or vitrectomy for microbial culture in order to determine the need for antibiotic treatment.

Review Article

A narrative review of glaucoma screening from fundus images

A narrative review of glaucoma screening from fundus images

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Abstract: The objective of the paper is to provide a general view for automatic cup to disc ratio (CDR) assessment in fundus images. As for the cause of blindness, glaucoma ranks as the second in ocular diseases. Vision loss caused by glaucoma cannot be reversed, but the loss may be avoided if screened in the early stage of glaucoma. Thus, early screening of glaucoma is very requisite to preserve vision and maintain quality of life. Optic nerve head (ONH) assessment is a useful and practical technique among current glaucoma screening methods. Vertical CDR as one of the clinical indicators for ONH assessment, has been well-used by clinicians and professionals for the analysis and diagnosis of glaucoma. The key for automatic calculation of vertical CDR in fundus images is the segmentation of optic cup (OC) and optic disc (OD). We take a brief description of methodologies about the OC and disc optic segmentation and comprehensively presented these methods as two aspects: hand-craft feature and deep learning feature. Sliding window regression, super-pixel level, image reconstruction, super-pixel level low-rank representation (LRR), deep learning methodologies for segmentation of OD and OC have been shown. It is hoped that this paper can provide guidance and bring inspiration to other researchers. Every mentioned method has its advantages and limitations. Appropriate method should be selected or explored according to the actual situation. For automatic glaucoma screening, CDR is just the reflection for a small part of the disc, while utilizing comprehensive factors or multimodal images is the promising future direction to furthermore enhance the performance.

Abstract: The objective of the paper is to provide a general view for automatic cup to disc ratio (CDR) assessment in fundus images. As for the cause of blindness, glaucoma ranks as the second in ocular diseases. Vision loss caused by glaucoma cannot be reversed, but the loss may be avoided if screened in the early stage of glaucoma. Thus, early screening of glaucoma is very requisite to preserve vision and maintain quality of life. Optic nerve head (ONH) assessment is a useful and practical technique among current glaucoma screening methods. Vertical CDR as one of the clinical indicators for ONH assessment, has been well-used by clinicians and professionals for the analysis and diagnosis of glaucoma. The key for automatic calculation of vertical CDR in fundus images is the segmentation of optic cup (OC) and optic disc (OD). We take a brief description of methodologies about the OC and disc optic segmentation and comprehensively presented these methods as two aspects: hand-craft feature and deep learning feature. Sliding window regression, super-pixel level, image reconstruction, super-pixel level low-rank representation (LRR), deep learning methodologies for segmentation of OD and OC have been shown. It is hoped that this paper can provide guidance and bring inspiration to other researchers. Every mentioned method has its advantages and limitations. Appropriate method should be selected or explored according to the actual situation. For automatic glaucoma screening, CDR is just the reflection for a small part of the disc, while utilizing comprehensive factors or multimodal images is the promising future direction to furthermore enhance the performance.

Review Article

Rapid retinal functional testing

Rapid retinal functional testing

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Abstract: The most prominent causes of loss of vision in individuals over 50 years include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). While it is important to screen for these diseases effectively, current eye care is not properly doing so for much of the population, resulting in unfortunate visual disability and high costs for patients. Innovative functional testing can be unified with other screening methods for a more robust and safer screening and prediction of disease. The goal in the creation of functional testing modalities is to develop highly sensitive screening tests that are easy to use, accessible to all users, and inexpensive. The tests herein are deployed on an iPad with easily understood and intuitive instructions for rapid, streamlined, and automatic administration. These testing modalities could become highly sensitive screenings for early detection of potentially blinding diseases. The applications from our collaborators at AMA Optics include a cone photostress recovery test for detection of AMD and diabetic macular edema (DME), brightness balance perception for optic nerve dysfunction and especially glaucoma, color vision testing which is a broad screening tool, and visual acuity test. Machine learning with the combined structural and functional data will optimize identification of disease and prediction of outcomes. Here, we review and assess various tests of visual function that are easily administered on a tablet for screening in primary care. These user-friendly and simple screening tests allow patients to be identified in the early stages of disease for referral to specialists, proper assessment and treatment.

Abstract: The most prominent causes of loss of vision in individuals over 50 years include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). While it is important to screen for these diseases effectively, current eye care is not properly doing so for much of the population, resulting in unfortunate visual disability and high costs for patients. Innovative functional testing can be unified with other screening methods for a more robust and safer screening and prediction of disease. The goal in the creation of functional testing modalities is to develop highly sensitive screening tests that are easy to use, accessible to all users, and inexpensive. The tests herein are deployed on an iPad with easily understood and intuitive instructions for rapid, streamlined, and automatic administration. These testing modalities could become highly sensitive screenings for early detection of potentially blinding diseases. The applications from our collaborators at AMA Optics include a cone photostress recovery test for detection of AMD and diabetic macular edema (DME), brightness balance perception for optic nerve dysfunction and especially glaucoma, color vision testing which is a broad screening tool, and visual acuity test. Machine learning with the combined structural and functional data will optimize identification of disease and prediction of outcomes. Here, we review and assess various tests of visual function that are easily administered on a tablet for screening in primary care. These user-friendly and simple screening tests allow patients to be identified in the early stages of disease for referral to specialists, proper assessment and treatment.

Review Article

Dealing with pediatric glaucoma: from medical to surgical management—a narrative review

Dealing with pediatric glaucoma: from medical to surgical management—a narrative review

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Abstract: Pediatric glaucoma is a potentially sight-threatening disease and is considered the second leading cause of treatable childhood blindness. Pediatric glaucoma is a clinical entity including a wide range of conditions: primary congenital glaucoma, glaucoma secondary to ocular (e.g., aniridia, Peter’s anomaly), or systemic disease (e.g., Sturge Weber) and glaucoma secondary to acquired condition (pseudophakic, traumatic, uveitic glaucoma). The treatment algorithm of childhood glaucoma is a step-by-step approach, often starting with surgery, as in primary congenital glaucoma cases. Medical therapy is also crucial in the management of pediatric glaucoma. Here we reported the results of the randomized, controlled, clinical trials carried out in children treated with topical anti-glaucoma drugs. It is worth knowing that prostaglandin analogues showed an excellent systemic safety profile, while serious systemic events have been reported in children taking topical beta-blockers. Angle surgery is the first surgical option in patients diagnosed with primary congenital glaucoma, with ab interno and ab externo approaches showing similar outcomes. Trabeculectomy in children can be troublesome, as mitomycin C (MMC) can lead to bleb complications and a higher endophthalmitis rate than in adults. Glaucoma drainage devices (GDD) are no longer a last resort and can be considered a suitable option for the management of uncontrolled pediatric glaucoma after angle surgery failure.

Abstract: Pediatric glaucoma is a potentially sight-threatening disease and is considered the second leading cause of treatable childhood blindness. Pediatric glaucoma is a clinical entity including a wide range of conditions: primary congenital glaucoma, glaucoma secondary to ocular (e.g., aniridia, Peter’s anomaly), or systemic disease (e.g., Sturge Weber) and glaucoma secondary to acquired condition (pseudophakic, traumatic, uveitic glaucoma). The treatment algorithm of childhood glaucoma is a step-by-step approach, often starting with surgery, as in primary congenital glaucoma cases. Medical therapy is also crucial in the management of pediatric glaucoma. Here we reported the results of the randomized, controlled, clinical trials carried out in children treated with topical anti-glaucoma drugs. It is worth knowing that prostaglandin analogues showed an excellent systemic safety profile, while serious systemic events have been reported in children taking topical beta-blockers. Angle surgery is the first surgical option in patients diagnosed with primary congenital glaucoma, with ab interno and ab externo approaches showing similar outcomes. Trabeculectomy in children can be troublesome, as mitomycin C (MMC) can lead to bleb complications and a higher endophthalmitis rate than in adults. Glaucoma drainage devices (GDD) are no longer a last resort and can be considered a suitable option for the management of uncontrolled pediatric glaucoma after angle surgery failure.

Review Article
Original Article
Original Article

Reconstruction of total lower eyelid defect—a case series

Reconstruction of total lower eyelid defect—a case series

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Background: Total lower eyelid defect after eyelid malignancy excision poses a challenge in the surgical management of total lower eyelid reconstruction. We describe a technique of reconstructing total lower eyelid defect, using a skin flap and the residual lower forniceal conjunctiva.

Methods: A retrospective case series review. Five patients had undergone lower eyelid basal cell carcinoma excision. A 3–4 mm margin excision was performed and specimens were sent for paraffin section histological examination. Reconstruction was performed at the same stage, using a skin flap and the residual lower forniceal conjunctiva. A full thickness skin flap is raised from the lateral cheek, with its base at the lateral canthus. Subcutaneous tissues are not included in the skin flap. The lower forniceal conjunctiva is released from the inferior retractors and advanced superiorly to cover the inner surface of the skin flap. The skin flap is transposed to cover the lower eyelid defect and sutured to the soft tissues at the medial end of the defect. The advanced forniceal conjunctiva is sutured to the superior edge of the skin flap forming the new mucocutaneous junction of the eyelid margin.

Results: There were 4 females and 1 male, with a mean age of 74 years (range, 68–80 years). Histological clearance was achieved in all cases. None of the patients developed lagophthalmos, symblepharon or dry eye symptoms. None of the patients required any further revision surgery.

Conclusions: Total lower eyelid defects can be reconstructed using the residual lower fornix conjunctiva and a skin flap.

Background: Total lower eyelid defect after eyelid malignancy excision poses a challenge in the surgical management of total lower eyelid reconstruction. We describe a technique of reconstructing total lower eyelid defect, using a skin flap and the residual lower forniceal conjunctiva.

Methods: A retrospective case series review. Five patients had undergone lower eyelid basal cell carcinoma excision. A 3–4 mm margin excision was performed and specimens were sent for paraffin section histological examination. Reconstruction was performed at the same stage, using a skin flap and the residual lower forniceal conjunctiva. A full thickness skin flap is raised from the lateral cheek, with its base at the lateral canthus. Subcutaneous tissues are not included in the skin flap. The lower forniceal conjunctiva is released from the inferior retractors and advanced superiorly to cover the inner surface of the skin flap. The skin flap is transposed to cover the lower eyelid defect and sutured to the soft tissues at the medial end of the defect. The advanced forniceal conjunctiva is sutured to the superior edge of the skin flap forming the new mucocutaneous junction of the eyelid margin.

Results: There were 4 females and 1 male, with a mean age of 74 years (range, 68–80 years). Histological clearance was achieved in all cases. None of the patients developed lagophthalmos, symblepharon or dry eye symptoms. None of the patients required any further revision surgery.

Conclusions: Total lower eyelid defects can be reconstructed using the residual lower fornix conjunctiva and a skin flap.

Editorial
Review Article
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    主办:中山大学
    承办:中山大学中山眼科中心
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    主管:中华人民共和国教育部
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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