Background: To evaluate efficacy and safety of combined pars plana vitrectomy (PPV) and scleral fixated intraocular lens (SFIOL) surgery as a single procedure.

Methods: Retrospective interventional case series done at a tertiary eye care center in Northern India. Eleven patients who underwent combined PPV and SFIOL surgery were included and analyzed retrospectively.

Results: Mean age of the patients was 43.36±15.12 years (range, 22–64 years). Eight were male. Mean baseline best corrected visual acuity (BCVA) was 0.78±0.63 logMAR units while the mean post-operative BCVA at 6 months follow-up was 0.37±0.29 logMAR units, the visual gain being statistically significant (P=0.021). None of the patients had a drop in BCVA with nine patients having final BCVA better than 0.48 logMAR units. Choroidal detachment (CD) was the only notable complication, seen in three patients. Other complications included two cases of intraoperative retinal breaks, a case each of reversible corneal edema, ocular hypertension and cystoid macular edema.

Conclusions: Combined PPV and SFIOL is an efficacious procedure for managing IOL/lens dislocation and aphakia in a single surgery. There may be short-term reversible complications with no impact on final visual gain.

Background: To evaluate efficacy and safety of combined pars plana vitrectomy (PPV) and scleral fixated intraocular lens (SFIOL) surgery as a single procedure.

Methods: Retrospective interventional case series done at a tertiary eye care center in Northern India. Eleven patients who underwent combined PPV and SFIOL surgery were included and analyzed retrospectively.

Results: Mean age of the patients was 43.36±15.12 years (range, 22–64 years). Eight were male. Mean baseline best corrected visual acuity (BCVA) was 0.78±0.63 logMAR units while the mean post-operative BCVA at 6 months follow-up was 0.37±0.29 logMAR units, the visual gain being statistically significant (P=0.021). None of the patients had a drop in BCVA with nine patients having final BCVA better than 0.48 logMAR units. Choroidal detachment (CD) was the only notable complication, seen in three patients. Other complications included two cases of intraoperative retinal breaks, a case each of reversible corneal edema, ocular hypertension and cystoid macular edema.

Conclusions: Combined PPV and SFIOL is an efficacious procedure for managing IOL/lens dislocation and aphakia in a single surgery. There may be short-term reversible complications with no impact on final visual gain.

Abstract: Tea is the second most popular beverage worldwide after water. Green tea has the highest nutraceutical values with well-established general health benefits and wide safety margins. Natural polyphenols found in green tea, including (+)-catechin (C), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (–)-epicatechin-3-gallate (ECG), (–)-gallocatechin-3-gallate (GCG) and (–)-epigallocatehin-3-gallate (EGCG). They have many potent biological properties and therapeutic effects in human health and diseases. These small molecules have high bioavailability and specific therapeutic potential in eye tissues. Recently some researchers studied the metabolomic responses to the green tea. In this talk, summary of these studies will be reviewed and its potential applications in the ocular research will be discussed.

Abstract: Tea is the second most popular beverage worldwide after water. Green tea has the highest nutraceutical values with well-established general health benefits and wide safety margins. Natural polyphenols found in green tea, including (+)-catechin (C), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (–)-epicatechin-3-gallate (ECG), (–)-gallocatechin-3-gallate (GCG) and (–)-epigallocatehin-3-gallate (EGCG). They have many potent biological properties and therapeutic effects in human health and diseases. These small molecules have high bioavailability and specific therapeutic potential in eye tissues. Recently some researchers studied the metabolomic responses to the green tea. In this talk, summary of these studies will be reviewed and its potential applications in the ocular research will be discussed.

Abstract: As a complex disease, myopia is the most common eye disease worldwide. Many myopia susceptibility genes or variants have been successfully identified in the past years by genome-wide genetic association studies (GWAS), which focus mainly on the single-nucleotide polymorphisms. Little attention has been paid to examine the role of copy number variations (CNVs) in refractive error and myopia. This study adopted a systematic strategy to investigate the role of CNVs in high myopia. In the discovery phase, a pilot GWAS suggests putative CNVs for follow-up. Multiplex ligation-dependent probe amplification was then used to quantify the copy number of 89 CNV segments in 737 case-control samples in the second phase and then 24 top-ranking CNVs in a second group of 1,029 case-control samples in the final validation phase. This validation phase identified 22 significant CNVs. Further work is needed to examine the role of these few CNVs in myopia development.

Abstract: As a complex disease, myopia is the most common eye disease worldwide. Many myopia susceptibility genes or variants have been successfully identified in the past years by genome-wide genetic association studies (GWAS), which focus mainly on the single-nucleotide polymorphisms. Little attention has been paid to examine the role of copy number variations (CNVs) in refractive error and myopia. This study adopted a systematic strategy to investigate the role of CNVs in high myopia. In the discovery phase, a pilot GWAS suggests putative CNVs for follow-up. Multiplex ligation-dependent probe amplification was then used to quantify the copy number of 89 CNV segments in 737 case-control samples in the second phase and then 24 top-ranking CNVs in a second group of 1,029 case-control samples in the final validation phase. This validation phase identified 22 significant CNVs. Further work is needed to examine the role of these few CNVs in myopia development.

Abstract: Retinal angiogenic diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) represent the leading causes of vision impairment in developed countries. There is strong evidence that dysregulated metabolic pathways contribute to DR as known risk factors do not explain all cases and the phenomenon of metabolic memory persists for decades or longer. Some early studies also showed that changes of plasma metabolic profiles are associated with AMD. Metabolic abnormalities can be explored using the techniques of the new science of metabolomics. In this presentation, several metabolomics workflows as well as the application of data independent acquisition mass spectrometry (DIA-MS) in metabolomics will be discussed. Our recent findings from metabolomics studies on DR and AMD will be presented.

Abstract: Retinal angiogenic diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) represent the leading causes of vision impairment in developed countries. There is strong evidence that dysregulated metabolic pathways contribute to DR as known risk factors do not explain all cases and the phenomenon of metabolic memory persists for decades or longer. Some early studies also showed that changes of plasma metabolic profiles are associated with AMD. Metabolic abnormalities can be explored using the techniques of the new science of metabolomics. In this presentation, several metabolomics workflows as well as the application of data independent acquisition mass spectrometry (DIA-MS) in metabolomics will be discussed. Our recent findings from metabolomics studies on DR and AMD will be presented.

Abstract: The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention. The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation. Using systematic and sensitive lipidomic approaches, we reported the most comprehensive human tear lipidome to date; and conferred novel insights to the compositional details of the existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-ω-hydroxy fatty acids, and various sphingolipids and phospholipids in tears. Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome (DES) revealed structure-specific lipid alterations in DES, which could potentially serve as unifying indicators of disease symptoms and signs.

The meibomian glands constitute the predominant source of lipid supply to the human tear fluid. Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and ocular discomfort, characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface. We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks. Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.

Abstract: The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention. The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation. Using systematic and sensitive lipidomic approaches, we reported the most comprehensive human tear lipidome to date; and conferred novel insights to the compositional details of the existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-ω-hydroxy fatty acids, and various sphingolipids and phospholipids in tears. Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome (DES) revealed structure-specific lipid alterations in DES, which could potentially serve as unifying indicators of disease symptoms and signs.

The meibomian glands constitute the predominant source of lipid supply to the human tear fluid. Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and ocular discomfort, characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface. We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks. Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.

Abstract: The translation of current tissue engineering approaches to clinical application is somehow limited by the use of scaffolding materials. Recently a number of in vitro scaffold-free three-dimensional culture techniques have been developed. These techniques realize the assembly of tissue-like structures including but not limited to spheroids, blood vessels and cartilage. In particular, cells can now self-assemble to form planar tissue-like structures at the interface of an aqueous-two-phase system (ATPS). The unique advantage of this technique is that without a solid substrate, planar tissue-like structures can now be assembled rapidly with very simple procedures. This technique can potentially be very useful for tissue engineering in eye because of its ability to direct cells to form monolayer. In this talk, we will introduce what ATPS is and its current applications in biomedical research. We will then present an approach to assemble cell sheets in ATPS using both primary cells isolated from porcine eyes and other cell lines. The physiological relevance of these eye-related cell sheets as well as their potentials in ophthalmic research and applications will be discussed.

Abstract: The translation of current tissue engineering approaches to clinical application is somehow limited by the use of scaffolding materials. Recently a number of in vitro scaffold-free three-dimensional culture techniques have been developed. These techniques realize the assembly of tissue-like structures including but not limited to spheroids, blood vessels and cartilage. In particular, cells can now self-assemble to form planar tissue-like structures at the interface of an aqueous-two-phase system (ATPS). The unique advantage of this technique is that without a solid substrate, planar tissue-like structures can now be assembled rapidly with very simple procedures. This technique can potentially be very useful for tissue engineering in eye because of its ability to direct cells to form monolayer. In this talk, we will introduce what ATPS is and its current applications in biomedical research. We will then present an approach to assemble cell sheets in ATPS using both primary cells isolated from porcine eyes and other cell lines. The physiological relevance of these eye-related cell sheets as well as their potentials in ophthalmic research and applications will be discussed.

Abstract: Encapsulated-cell therapy (ECT) is an attractive approach for continuously delivering freshly synthesized therapeutics to treat sight-threatening posterior eye diseases, circumventing repeated invasive intravitreal injections and improving local drug availability clinically. Composite collagen-alginate (CAC) scaffold in ECT contains an interpenetrating network that integrates the physical and biological merits of its constituents, including biocompatibility, mild gelling properties and availability. An injectable CAC system that supported the growth of HEK293 cells with sustainable glial-derived neurotrophic factor (GDNF) delivery has been developed. Continuous GDNF delivery was detected in culture and in healthy rat eyes for at least 14 days. The gels were well tolerated with no host tissue attachment and contained living cell colonies. Most importantly, gel implantation in dystrophic Royal College of Surgeons rat eyes for 28 days retained photoreceptors while those gels containing higher initial cell number yielded better photoreceptor rescue effect. This rescue effect is clinically relevant as photoreceptor death is a common pathology in many retinal diseases. Moreover, since cells including autologous cells can be genetically engineered to secrete various therapeutic agents, CAC gel offers a flexible system design and is a potential treatment option for other chronic neurodegenerative diseases.

Abstract: Encapsulated-cell therapy (ECT) is an attractive approach for continuously delivering freshly synthesized therapeutics to treat sight-threatening posterior eye diseases, circumventing repeated invasive intravitreal injections and improving local drug availability clinically. Composite collagen-alginate (CAC) scaffold in ECT contains an interpenetrating network that integrates the physical and biological merits of its constituents, including biocompatibility, mild gelling properties and availability. An injectable CAC system that supported the growth of HEK293 cells with sustainable glial-derived neurotrophic factor (GDNF) delivery has been developed. Continuous GDNF delivery was detected in culture and in healthy rat eyes for at least 14 days. The gels were well tolerated with no host tissue attachment and contained living cell colonies. Most importantly, gel implantation in dystrophic Royal College of Surgeons rat eyes for 28 days retained photoreceptors while those gels containing higher initial cell number yielded better photoreceptor rescue effect. This rescue effect is clinically relevant as photoreceptor death is a common pathology in many retinal diseases. Moreover, since cells including autologous cells can be genetically engineered to secrete various therapeutic agents, CAC gel offers a flexible system design and is a potential treatment option for other chronic neurodegenerative diseases.

Abstract: Animals promote their survival by avoiding rapidly approaching objects that indicate threats. It is believed that looming cues are detected by retinal ganglion cells (RGCs) that project to the superior colliculus (SC). However, the exact type of RGC that transmits looming-related signals remains unclear. Here we identify a specific transient type of RGCs that controls mouse looming-evoked defensive response by sending axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABA neurons and in turn inhibit serotonin neurons. Moreover, optogenetically stimulating serotonin neurons reduces looming-evoked defensive behaviors. Thus, a dedicated population of RGCs detects rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how DRN and SC work in concert to extract and translate visual threats into defensive behavioral responses.

Abstract: Animals promote their survival by avoiding rapidly approaching objects that indicate threats. It is believed that looming cues are detected by retinal ganglion cells (RGCs) that project to the superior colliculus (SC). However, the exact type of RGC that transmits looming-related signals remains unclear. Here we identify a specific transient type of RGCs that controls mouse looming-evoked defensive response by sending axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABA neurons and in turn inhibit serotonin neurons. Moreover, optogenetically stimulating serotonin neurons reduces looming-evoked defensive behaviors. Thus, a dedicated population of RGCs detects rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how DRN and SC work in concert to extract and translate visual threats into defensive behavioral responses.