The cornea is the most outer structure of the eye. What makes the cornea unique is that it is avascular, transparent, and potentially one of the most innervated tissues in the human body. As a key component of vision, proper health measures are needed to ensure its functionality and survival. Continuous corneal trauma, as a result of accidental wounding or disease, can potentially lead to partial or total vision loss. It has been shown that diseases such as obesity and diabetes can induce a state of hypoxia and alter substrate stiffness. It was hypothesized that corneal cells under normoxic conditions will experience morphological changes in response to substrate stiffness and matrix proteins compared to corneal cells exposed to hypoxic conditions where cells will respond differently as a result of environment. Results showed that the morphology of corneal cells exposed to normoxic conditions were more influenced by substrate stiffness and that corneal cells exposed to hypoxic conditions displayed characteristic signs of cellular senescence.

The purpose of this study is to evaluate the effectiveness of pars plans vitrectomy with relaxing retinectomy as treatment for recurrent rhegmatogenous retinal detachments (RRD) complicated by proliferative vitreoretinopathy (PVR).  This retrospective case series was conducted with data from a single retina surgeon at Beth Israel Deaconess Medical Center. The medical records of 101 patients who underwent pars plana vitrectomy (PPV) with relaxing retinectomy for retinal detachment with PVR between January 2006 and August 2016 were identified. Exclusionary criteria eliminated patients with proliferative diabetic retinopathy, tractional retinal detachments, and open globe trauma, leaving a total of 57 participants (n=57 eyes) with rhegmatogenous retinal detachment complicated by PVR of grade C or more. All participants were initially treated with three-port PPV with membrane peeling combined with relaxing retinectomy, barrier endolaser photocoagulation, and silicone oil tamponade (n=48) or gas tamponade with SF6 (n=7) or C3F8 (n=2). The primary outcome measures were complete retinal reattachment for a minimum of 3 months and final visual acuity. Final anatomical success was achieved in all 57 patients. Successful reattachment was observed after one surgery in 40 of 57 eyes (70.2%). Sixteen of the 17 re-detachments were successfully reattached after one reoperation. One case required a third surgery to achieve complete reattachment. Four patients developed hypotony defined as intraocular pressure (IOP) < 5 mmHg (7%). A significant difference between pre- and postoperative best corrected visual acuity (BCVA) was defined as a change by at least 2 snellen lines. Of the 50 patients for whom BCVA was documented, visual acuity improved in 27 patients (63%), remained the same in 10 patients (23%), and worsened 6 patients (14%). Thirty-seven (87%) participants overall were had visual acuity greater or equal to 5/200 at 3-months post-operatively. Our study demonstrated good anatomic and visual outcomes after retinectomy for patients with RRD associated with PVR, which were significantly better than outcomes in the Silicone Oil Study Report 5. The high rate of success reported in our study is likely due to improved technology and techniques, and possibly the proactive use of retinectomy in less severe cases of PVR. The results of our study demonstrate that the use of relaxing retinectomy in patients with RRD and PVR provides an effective method for definitively relieving retinal traction and improving anatomic and visual outcomes. / 2019-07-11T00:00:00Z

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The overall goal of this research is to alleviate suffering and improve visual outcomes for burn patients during recovery, using amniotic membrane as a stabilized 'patch' for the corneal surface. Second and third degree facial burns result in scarring, which can lead to contraction of tissues around the eyelids, a condition called ectropion. This renders the burn patient unable to close their eyes or blink, which can be followed by loss of moisture, breakdown of defense mechanisms, permanent scarring and opacification of the cornea. Instead of continuously applying artificial tears to these victims' eyes, which would actually slow rate of recovery, the use of amniotic membrane would help seal in moisture as well as increase the rate of recovery, while not compromising corneal clarity. However, due to enzymes in the tears of inflamed eyes, the amniotic membrane is degraded fairly rapidly. It is the goal of this team's research efforts to determine an efficient way to stabilize the amniotic membrane by cross-linking its constitutive proteins, so that the rate of amnion degradation by enzymes is decreased but the levels of various beneficial pro-healing factors are preserved. While work is being done to assess the effects of cross-linking on the rate of amnion degradation, this study focused on the effects of protein crosslinking on the levels of transforming growth factor-beta (TGF-ß 1 ), one of the most abundant growth factors in human amniotic membrane. A specific protocol utilizing liquid nitrogen for the homogenization of de-epithelialized and cryopreserved human amniotic membrane (HAM) was created. TGF-ß 1 content in untreated, carbodiimide cross-linked, and photochemical tissue bonding (PTB) cross-linked HAM samples was measured using enzyme-linked immunoasorbent assay (ELISA). It was shown that while the stability of the membrane due to cross-linking of the collagen in the treated samples was increased, the protein content was severely affected; TGF-~1 levels in highly crosslinked HAM samples were extremely lower than that of the untreated. It was also demonstrated via ELISA that decreasing the extent of protein crosslinking by varying the treatment time with carbodiimide or decreasing the fluence of the light used in PTB resulted in equally stabilized amniotic membrane, but higher TGF-ß 1 content than in previously treated samples. This signifies that both chemical and photochemical protocols can result in beneficial collagen cross-linking, and potentially preserve the helpful growth factors already inherent in HAM for use in ophthalmology. / 2031-01-01

PURPOSE: To determine if there is a relationship between eyes with flat corneas (as defined by calculated postoperative keratometry values of <38D) undergoing either LASIK (Laser-assisted in Situ Keratomileusis), LASEK (Laser-assisted Subepithelial Keratectomy), or PRK (Photorefractive Keratectomy) corneal refractive surgery and loss of 1 or more lines of postoperative BCVA, and if there is an advantage to undergoing either LASIK or ASA in eyes meeting flat cornea criteria. METHODS: A retrospective analysis of 191 candidate eyes with calculated postoperative keratometry values <38D were identified and matched by manifest refraction and surgery type to 191 control eyes with calculated postoperative keratometry values ≥38D. Both candidate groups and control groups were further stratified into subgroups based on degree of calculated postoperative keratometry. Candidate subgroups: Subgroup 1a (K<35D), Subgroup 2a (K=35-35.99D), Subgroup 3a (K=36-36.99D), and Subgroup 4a (K=37-37.99D). Control subgroups: Subgroup 1b (K=38-38.99D), Subgroup 2b (K=39-39.99D), Subgroup 3b (K=40-40.99D) and Subgroup 4b (K≥41D). All patients had undergone corneal refractive eye surgery procedures LASIK, LASEK, or PRK at Boston Eye Group/Boston Laser in Brookline MA between December 2008 and November 2016. All LASIK flaps were created using the femtosecond laser IntraLase iFS60 Laser (Abbott Medical Optics Inc.). All surface ablation procedures were performed using the excimer lasers VISX STAR S4 IR Excimer Laser System (Abbot Medical Optics Inc.) or WaveLight EX500 Excimer Laser (Alcon Laboratories Inc.). Visual acuity outcomes measuring preoperative and postoperative BCVA and loss of BCVA were recorded as part of the patient’s medical chart and were statistically analyzed to determine correlations. RESULTS: Our data showed no significant differences between overall candidate (K<38D) and control (K≥38D) group mean preoperative BCVA (p<0.23) or mean postoperative BCVA (p<0.13). A total of 15 out of 191 (7.9%) candidate eyes lost 1 or more lines of BCVA in comparison to 23 total control eyes (12.0%) that lost 1 or more lines of BCVA postoperatively. When evaluating subgroup data, Candidate Subgroup 1a (K<35D) showed a significant (p<0.02) decrease in BCVA when compared to other candidate subgroups. Additionally, Control Subgroup 1b (K=38=38.99D) and Control Subgroup 2b (39-39.99D) showed a significant (p<0.001 and p<0.02 respectively) decrease in BCVA compared to other control subgroups. A total of 231 total candidate and control eyes underwent LASIK and a total of 151 total candidate and control eyes underwent ASA. Overall, 17 out of the 231 (7.4%) eyes undergoing LASIK lost BCVA compared to the 21 out of 151 (13.9%) eyes undergoing ASA that lost BCVA which was significant (p<0.04). CONCLUSION: This study did not find evidence to support that the overall flat cornea group (K<38D) lost postoperative BCVA when compared to a control group of eyes with normal keratometry values. However, our data indicated that when the candidate group was stratified by degree of corneal curvature, patients with very flat corneas (K<35D) may be at increased risk of losing BCVA though further studies are needed. Additionally, eyes undergoing ASA may be at increased risk of losing BCVA though further studies are needed. / 2018-07-11T00:00:00Z

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

SPECIFIC AIM: Worldwide, there is a deficiency in the availability and the outcomes of corneal transplants procedures. The use of sutures in the various types of corneal transplant procedures increases the skill requirements for performing the procedure in addition to bringing about various suture-related complications. In order to avoid these complications and to make the procedure easier to perform, it is vital to review the properties and availability of various surgical adhesives in order to assess their potential as candidates for replacing suture use in corneal transplant procedures. The focus in this paper will be on the most prominent of these procedures: the penetrating keratoplasty procedure. RECENT FINDINGS: Surgical adhesives that could potentially act as replacements or adjuncts to suture use in the penetrating keratoplasty procedure include homologous fibrin adhesives, polyethylene glycol sealants, cyanoacrylate glue, and poly [glycerol-sebacate-acrylate] (PGSA) glue. Polyethylene glycol sealants, when used as adjuncts to suture use in keratoplasty procedures lead to significant levels of wound dehiscence. Fibrin glues have been found to reduce the amount of sutures required in a "top hat" wound configuration penetrating keratoplasty when used as an adjunct to sutures in binding the donor button in place. Cyanoacrylate glues, although having higher levels of adhesive strength than fibrin glue, lead to various unwanted side effects. Lastly, PGSA glue, given its recent development, remains an uncertainty due to the lack of research on it. SUMMARY: Overall, use of homologous fibrin glues is currently the most likely way to reduce the use of sutures in the penetrating keratoplasty procedure. Its use could lead to shorter operative times, fewer complications, reductions in cost, and higher availability for corneal transplant procedures. However, with further investigation, PGSA glue may prove to be a better candidate for the replacement of sutures than fibrin glues.

OBJECTIVE: The main function of the human eye is to detect light, motion, and color from our surroundings. This information is then processed and translated in the brain as vision. However, what is less known about the eye is its ability to regulate immune function. It is this ocular immune privilege that maintains the eye's ability collect visual information. The degeneration of immune privilege causes inflammation, which can cause damage to the eye, an increased susceptibility of eye disorders such as autoimmune uveitis (inflammation of the uvea), and may lead to vision impairment. Research in ocular immune privilege can open up potential clinical applications for maladies such as uveitis, septic shock, hypersensitivity, multiple sclerosis and allograft survival. Previous research has shown the importance of the retinal pigment epithelial (RPE) cells for maintenance of ocular immune privilege, and has identified the use of neuropeptides to suppress inflammatory responses in macrophages. This project aims to study the role and mechanism of the RPE cells in phagolysosome activation in macrophages that mediate inflammation. METHODS: Posterior eyecups were prepared from eyes of healthy, EAU immunized, or post-EAU mice. Eyecups, which consisted of the sclera, choroid, and a single layer of RPE, were cultured in serum-free media (SFM). During a 24-hour incubation period, peritoneal macrophages were collected intraperitoneal (IP) and cultured. Conditioned media (CM) was applied to the collected macrophages along with pHrodo-red opsonized bioparticles and were incubated for 24-hours in 37°C. After incubation, cells were examined by fluorescent microscopy for phagolysosome activation. Also, this was also done with RPE CM depleted of α-MSH, NPY, and α-MSH + NPY. A viability assay was performed on macrophages treated with depleted RPE CM to investigate the possibility that removing the neuropeptides will induce cell death. To examine the cytokines involved in RPE CM--from healthy, EAU and post-EAU mice--modulation of phagolysosome activation, a mouse cytokine array was performed that assessed for twenty different mouse cytokines. RESULTS: Results from fluorescent microscopy showed that healthy RPE CM caused significant suppression of phagolysosome activity in macrophages. The RPE CM depleted of α-MSH, NPY, and α-MSH + NPY showed a significant suppression of phagolysosome activity in macrophages. However, these results may have been misrepresented as the macrophages treated with depleted RPE CM were non-viable. RPE CM from EAU mice showed the inability to down-regulate phagolysosome activity while RPE CM from post-EAU mice recovered its ability to down-regulate phagolysosome activity. The mouse cytokine array of RPE CM from healthy, EAU and post-EAU mice identified keratinocyte-derived cytokine (KC), high concentrations of interleukin-6 (IL-6), trace amounts of vascular endothelial growth factor (VEGF), and no other pro or anti-inflammatory cytokines. CONCLUSIONS: Healthy RPE cells suppress phagolysosome activation in activated macrophages. In contrast, RPE cells from mice with active EAU lose its ability to regulate phagolysosome activation, but regain this ability when the disease resolves following α-MSH treatment. RPE CM from post-EAU mice treated with MC5r agonist did not recover suppression of phagolysosome activation which suggests that α-MSH causes suppression of phagolysosome activation through other melanocortin receptors or that this suppression requires other mechanisms in conjunction to MC5r stimulation. Cytokine IL-6 may be involved in RPE suppression of phagolysosome activation; however, further study will have to be done. The results demonstrate that part of the mechanisms of ocular immune privilege is the tight control by RPE of the phagocytic process in macrophages. It is possible that this contributes to ocular immune privilege minimizing the potential of processing and presenting self-proteins, and to allow for clearance of harmful materials while suppressing the activation of inflammation.

PURPOSE: To investigate the outcomes and success rate of surgical intervention for patients diagnosed with primary rhegmatogenous retinal detachment. We investigate the most common and current procedures: pneumatic retinopexy (PR), pars plana vitrectomy(PPV), scleral buckle(SB), and combined vitrectomy and scleral buckle(SB+PPV). METHODS: This nonrandomized, retrospective case series was conducted using data from a single retina surgeon at Beth Israel Deaconess Medical Center. Patient data was collected from September 1999 - October 2017. The main inclusion criteria were diagnosis with a primary (meaning it is a first RD experienced by the eye) RRD and subsequent treatment with scleral buckle, vitrectomy, pneumatic retinopexy, or a combination of scleral buckle and vitrectomy (SBV). Patients who have experienced a prior RD, trational RD, or RD due to trauma were excluded from this study. Preoperative and postoperative VA was compared using a logarithm of the minimum angle of resolution (logMAR) score. sixty patients underwent PR treatment (n=60), sixty patients were treated with a combination of SB+PPV (n=60), fifty-two were treated with PPV (n=52) alone, and fifty-four had SB (n=54) treatment. A successful outcome was a complete reattachment of the retina in subsequent follow-up appointments based on comprehensive fundus exams and ocular coherence tomography (OCT) scan. RESULTS: Our study showed significant success rates across all four potential surgeries. PR having a success rate of 48/60 (72%), SB+PPV with 53/60 (88%), PPV at 41/52 (77%), and SB showing 41/54 (79%). Starting visual acuity for PR was .67, Combined SB+PPV patients started with 1.4, PPV patients had a 1.84 logMAR score, and SB patients had a starting visual of 1.82. Patients undergoing PR treatment had a lower occurrence of mac-off RRD at 55%. While patients who underwent combined SB+PPV, vitrectomy alone, and SB had higher rates of mac-off RRD at 67%, 60%, and 58% respectively. CONCLUSIONS: Our study demonstrated good outcomes for all surgical procedures used. While the type of surgery performed will depend on a case-by-case determination. The results of our study showed improvement in visual acuity in patients after treatment for primary rhegmatogenous retinal detachment (RRD). Overall, the results of our study demonstrate very good outcomes for patients treated with PR, vitrectomy, SB, and combine SB+PPV.

This thesis examines the mechanisms of cone dysfunction in two different inherited retinal diseases: Achromatopsia and Retinitis Pigmentosa (RP). The first, minor, component of the thesis explored and characterised the loss of cone function in a novel mouse model of achromatopsia (cpfl10). The second, major, component of the thesis explored the loss of cone function in a mouse model of RP. I hypothesised that the cone function lost in RP could be restored using AAV vectors to over-express down regulated cone genes. This thesis subsequently developed and tested two AAV vectors delivering CRX and OPN1LW genes to photoreceptors in RP mice. Achromatopsia is a congenital condition characterised by absent or diminished cone function due to mutations of a single gene, typically those involved in the cone phototransduction cascade. This thesis provides a detailed phenotype of a novel cpfl10 mouse model of Achromatopsia that arose spontaneously in a local mouse colony. The causative (NM_013927)c.692G>A; p.(R231H) missense mutation in Cngb3 was also identified and explored. Retinitis pigmentosa (RP) is an inherited retinal degeneration in which secondary loss of cones follows the initial death of genetically abnormal rod photoreceptors. Strategies to prolong cone photosensitivity or survival would offer an important treatment. Such universal interventions could be effective regardless of which genetic mutation is underlying primary rod death. The molecular mechanisms by which cone photoreceptors lose photosensitivity in RP are poorly understood. I examined the gene expression profile of the cone phototransduction cascade in the Rho^-/- mouse model of RP and correlated these changes to declining retinal function. The cone opsins were substantially down-regulated, as was the photoreceptor transcription factor Crx. I hypothesised that the cone function lost in RP could be restored using AAV vectors to over-express these down regulated cone genes. Using an AAV gene therapy vectors, I delivered the human homologs CRX and OPN1LW to the retinas of the same Rho^-/- mouse model. Both vectors successfully transduced photoreceptors and RPE cells across three different doses. Transduced retinas did not show any improvement in cone function or survival. Whilst the observed down-regulation of cone genes correlates with cone function loss, it appears that both down-regulation and dysfunction arise from an unknown common cause. Ongoing research into mechanisms of metabolic starvation, oxidative stress and trophic factors in cone cell death offer promise for a common intervention to rescue cone photoreceptors.

Background: Penetrating trauma can have devastating visual consequences and is often challenging to manage effectively, especially in the setting of severe trauma. The decision to perform a primary repair or a primary evisceration following an open globe injury can be a difficult one. Removal of an eye is not only traumatic but produces grief, anxiety and depression. It can result in a poor quality of life of the affected patients, and thus must be justified before it is performed. Before a primary evisceration can be considered, certain criteria need to be fulfilled. The affected eye must have acuity of no perception of light. A total afferent pupillary defect must be present. There must be prolapsed uvea and/or retina in the wound. Wounds should be longer than 20mm, or extend posterior to the equator of the globe. The fellow eye should be normal and the patient must be able to give informed consent. The primary evisceration rete at Groote Schuur Hospital appears to be higher than in other centers. If we do conform to the required criteria, then we are justified in performing primary eviscerations, but if we do not conform, then we need to improve our adherence in order to meet the required standards and improve our management. Purpose: a. To determine if the above criteria for primary evisceration are met in those undergoing primary eviscerations at Groote Schuur Hospital, and at which point(s) we strayed from the guidelines. b. To determine the rate of primary and secondary eviscerations following ocular trauma. c. To evaluate the visual outcomes, at 3 months, of patients who present with no perception of light vision and total afferent pupillary defect who meet some of the criteria for primary evisceration, but primary evisceration is not performed. Methods: A retrospective case series study was performed to identify all patients who were admitted to the ophthalmology ward at Groote Schuur Hospital following an open globe injury. The records of all patients who underwent primary evisceration were analyzed to evaluate whether or not the criteria were met and to determine the rates of primary and secondary evisceration at GSH. Results: There was a total of 249 open globe injuries admitted during the designated two year period. Of these, 212 (85.14%) were males and 37 (14.86%) were females. The number of patients undergoing primary evisceration was 61 (24.5%) and the number of patients undergoing primary repair was 175 (70.3%) and thirteen (5.2%) had other procedures. Of the 61 patients who underwent primary evisceration, 10 patients had missing data and were thus excluded. Therefore, out of 51 patients in whom the required data was available, a total of 37 (72.55%) patients met ALL the criteria required for a primary evisceration to be performed. A total of 11 (21.56%) patients did not meet the visual acuity criterion of no perception of light (10 were perception of light and 1 was hand movements vision). A total of 9 (17.6%) patients were documented to not have a total relative afferent pupillary defect. All patients had prolapsed uvea in the wound. Three patients (5.8%) had an "abnormally" seeing or poorly seeing fellow eye. Five (9.8%) were not documented as irreparable. The informed consent criterion was fulfilled in all patients. Secondary eviscerations accounted for 4.6% of surgeries done for open globe trauma. Of the patients that were eligible for primary evisceration, but instead had primary repair, the majority (77.7%) remained NPL and 88.8% had phthisis bulbi at 3 months. Conclusion: The majority of our evisceration cases met all the criteria for a primary evisceration. The two criteria which we did not fully adhere to were the visual acuity of no light perception and the presence of a total relative afferent pupillary defect. Visual acuity testing in the trauma setting is challenging, but we should improve on the accuracy of our testing of these two entities, and clearer documentation of all the criteria in our open globe injury cases especially if undergoing a primary evisceration. A few patients had an abnormally seeing fellow eye and still underwent PE due to the injured eye being irreparable. Our primary evisceration rate reflects our resource- limited setting and the severity of our ocular trauma cases. The poor visual acuity and poor outcome in the form of phthisis bulbi at three months in those who did not have a primary evisceration despite poor acuity appears to support our rationale for performing primary eviscerations in those with poor prognoses, given our resourcelimited setting.